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Milla CE. The globalization of cystic fibrosis care. Curr Opin Pediatr 2025; 37:266-271. [PMID: 40172290 PMCID: PMC12055477 DOI: 10.1097/mop.0000000000001458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2025]
Abstract
PURPOSE OF REVIEW The field of cystic fibrosis is experiencing dramatic changes, as the translation of a massive body of scientific knowledge accumulated from the day of the cloning of the CFTR gene has led to the identification of effective therapies to correct the basic defect. This has also allowed care providers and people with cystic fibrosis in low-income and middle-income countries (LMICs) to become more knowledgeable and proficient in cystic fibrosis cares. RECENT FINDINGS This review focuses on two main aspects highly relevant to understand the current status of cystic fibrosis in LMICs: The recognition of the universal occurrence of cystic fibrosis, as well as the varying incidence in different regions of the world, and the collaborative international efforts for dissemination of best care practices as an attempt to close gaps in care. SUMMARY As the field continues to change rapidly, multiple international efforts are attempting to close gaps and disparities clearly apparent between affluent countries and LMICs. However, these efforts are seriously hampered by limited access to effective therapies and most dramatically to CFTR modulator drugs.
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Affiliation(s)
- Carlos E Milla
- Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Palo Alto, California, USA
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Li J, Zhang L, Xi F, Lin C, Zhan Q, Zhou Q, Zheng S, Chen W, Jin F. The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families. Hum Genomics 2025; 19:25. [PMID: 40075526 PMCID: PMC11905445 DOI: 10.1186/s40246-025-00736-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 02/23/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes. METHODS This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes. RESULTS Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39-8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050). CONCLUSION These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.
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Affiliation(s)
- Jingping Li
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
| | - Lingyun Zhang
- Department of Obstetrics and Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310025, China
| | - Fangfang Xi
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
| | - Chuanping Lin
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
- Department of Gynecology and Obstetrics, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325024, China
| | - Qitao Zhan
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
| | - Qing Zhou
- BGl Research, Shenzhen, 518083, China
| | - Shi Zheng
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
- Department of Obstetrics and Gynecology, Women And Children's Hospital of Ningbo University, Ningbo, 315012, China
| | - Weikang Chen
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China
| | - Fan Jin
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People's Republic of China.
- Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, 310006, China.
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Sun J, Hua L, He Y, Liu H, Liu Q, Chen M, Li J, Ye J, Fang D, Ji R, Chen Y, Yang C, Zhang J. Genetic analysis and functional study of novel CFTR variants in Chinese children with cystic fibrosis. Gene 2024; 907:148190. [PMID: 38246579 DOI: 10.1016/j.gene.2024.148190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 12/27/2023] [Accepted: 01/17/2024] [Indexed: 01/23/2024]
Abstract
OBJECTIVES To describe the clinical characteristics of Chinese cystic fibrosis (CF) patients and to investigate the variants of CFTR and their potential pathogenicity. STUDY DESIGN Chinese patients with potential CF diagnosis were studied. Clinical data were reviewed retrospectively from medical records. Whole exome sequencing and genetic evaluation were conducted to explore potential gene variants. The disruption of the variants to protein structure and function was explored and validated using in vitro experiments and in silico analysis. RESULTS Four patients were recruited to the study, three of them were diagnosed as CF, and one was diagnosed as CFTR-related disorder. The age at symptom onset for the patients in this study ranged from newborn to 6 years, while the age at diagnosis varied from 3 to 11 years. All four patients exhibited bilateral diffuse bronchiectasis with Pseudomonas aeruginosa infections, and three of them had malnutrition. Finger clubbing was observed in three patients, two of whom displayed mixed ventilatory dysfunction. The CFTR variants spectrum of Chinese children with CF differs from that of Caucasian. A total of six variants were identified, two of which were first reported (c.1219G > T [p.Glu407*] and c.1367delT [p.Ala457Leufs*12]). The nonsense variants c.1219G > T, c.1657C > T and c.2551C > T and the frameshift variant c.1367delT were predicted to introduce premature stop codon and produce shorten CFTR protein, which was also first validated by in vitro truncation assay in this study. The missense variant c.1810A > C was predicted to disrupt the function of the nucleotide-binding domain 1 (NBD1) in the CFTR protein. The splicing variant c.1766 + 5G > T caused skipping of exon 13 and damaged the integrity of CFTR protein. CONCLUSIONS Our study expands the spectrum of phenotypes and genotypes for CF of Chinese origin, which differs significantly from that of Caucasian. Genetic analysis and counseling are crucial and deserve extensive popularization for the diagnosis ofCF in patients of Chinese origin.
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Affiliation(s)
- Jingyi Sun
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Hua
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yafang He
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haipei Liu
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Quanhua Liu
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengxue Chen
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Li
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianmin Ye
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dingzhu Fang
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruoxu Ji
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Chen
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chao Yang
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
| | - Jianhua Zhang
- Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Abou Tayoun AN. Unequal global implementation of genomic newborn screening. Nat Rev Genet 2023; 24:801-802. [PMID: 37723349 DOI: 10.1038/s41576-023-00654-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Affiliation(s)
- Ahmad N Abou Tayoun
- Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
- Center for Genomic Discovery, Mohammed bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
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Abubakar Bobbo K, Ahmad U, Chau DM, Nordin N, Abdullah S. A comprehensive review of cystic fibrosis in Africa and Asia. Saudi J Biol Sci 2023; 30:103685. [PMID: 37313453 PMCID: PMC10258508 DOI: 10.1016/j.sjbs.2023.103685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 04/30/2023] [Accepted: 05/15/2023] [Indexed: 06/15/2023] Open
Abstract
Cystic fibrosis (CF) was earlier thought to be a disease prevalent in the West among Caucasians. However, quite a number of recent studies have uncovered CF cases outside of this region, and reported hundreds of unique and novel variant forms of CFTR. Here, we discuss the evidence of CF in parts of the world earlier considered to be rare; Africa, and Asia. This review also highlighted the CFTR mutation variations and new mutations discovered in these regions. This discovery implies that the CF data from these regions were earlier underestimated. The inadequate awareness of the disease in these regions might have contributed towards the poor diagnostic facilities, under-diagnosis or/and under-reporting, and the lack of CF associated health policies. Overall, these regions have a high rate of infant, childhood and early adulthood mortality due to CF. Therefore, there is a need for a thorough investigation of CF prevalence and to identify unique and novel variant mutations within these regions in order to formulate intervention plans, create awareness, develop mutation specific screening kits and therapies to keep CF mortality at bay.
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Affiliation(s)
- Khadijat Abubakar Bobbo
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
- Department of Human Anatomy College of Medical Sciences, Faculty of Medicine, Gombe State University, 760253 Gombe State, Nigeria
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
| | - Umar Ahmad
- Molecular Genetics Informatics, Department of Anatomy, Faculty of Basic Medical Sciences, Bauchi State University, 751105 Gadau, Nigeria
- Institute of Pathogen Genomics, Africa Centres for Disease Control and Prevention (Africa CDC), African Union Commission, P.O.Box 3243, Addis Ababa, Ethiopia
| | - De-Ming Chau
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
- Genetics & Regenerative Medicine Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
| | - Norshariza Nordin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
- Genetics & Regenerative Medicine Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
| | - Syahril Abdullah
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
- Genetics & Regenerative Medicine Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Selangor, Malaysia
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Shen Y, Tang X, Chen Q, Xu H, Liu H, Liu J, Yang H, Li H, Zhao S. Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China. J Med Genet 2022; 60:jmedgenet-2022-108501. [PMID: 35858753 PMCID: PMC9985745 DOI: 10.1136/jmg-2022-108501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 07/03/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND AND OBJECTIVES Cystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children. METHODS We recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children's Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised. RESULTS 158 different variants including 23 novel observations were identified after sequencing. The majority of CFTR variants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718-2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese. CONCLUSIONS The genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.
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Affiliation(s)
- Yuelin Shen
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Xiaolei Tang
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Qionghua Chen
- Quanzhou Children's Hospital, Quanzhou, People's Republic of China
| | - Hui Xu
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Hui Liu
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Jinrong Liu
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Haiming Yang
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Huimin Li
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
| | - Shunying Zhao
- Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China
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Kim JW. Pathogenic Variants Spectrum and Allele Frequency of the CFTR Gene in Asians. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2022; 14:444-446. [PMID: 36174988 PMCID: PMC9523414 DOI: 10.4168/aair.2022.14.5.444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 08/30/2022] [Indexed: 12/03/2022]
Affiliation(s)
- Jong-Won Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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8
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Shum BOV, Bennett G, Navilebasappa A, Kumar RK. Racially equitable diagnosis of cystic fibrosis using next-generation DNA sequencing: a case report. BMC Pediatr 2021; 21:154. [PMID: 33789612 PMCID: PMC8011156 DOI: 10.1186/s12887-021-02609-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 03/11/2021] [Indexed: 12/03/2022] Open
Abstract
Background Cystic Fibrosis (CF) is one of the most prevalent autosomal recessive inherited disease in Caucasians. Rates of CF were thought to be negligible in non-Caucasians but growing epidemiological evidence shows CF is more common in Indian, African, Hispanic, Asian, and other ethnic groups than previously thought. Almost all second-tier molecular diagnostic tools currently used to confirm the diagnosis of CF consist of panels of the most common CF-causing DNA variants in Caucasians. However non-Caucasian individuals with CF often have a different spectrum of pathogenic variants than Caucasians, limiting the clinical utility of existing molecular diagnostic panels in this group. As a consequence of racially inequitable CF testing frameworks, non-Caucasians with CF encounter greater delays in diagnosis and associated harms than Caucasians. An unbiased approach of detecting CF-causing DNA variants using full gene sequencing could potentially address racial inequality in current CF testing. Case presentation We present the case of a female baby from rural India who had a borderline first-tier newborn screening result for CF. Instead of choosing a targeted CF panel for second-tier testing, we used next-generation DNA sequencing to comprehensively analyze the cystic fibrosis transmembrane conductance regulator gene as an unbiased approach for molecular confirmation of CF. Sequencing identified two pathogenic variants that cause CF. One variant (c.1521_1523delCTT) is the most common cause of CF, while the other variant (c.870-1G > C) is absent from all population allele databases and has not been found in the Indian population previously. The rare variant would not have been detected by all currently available targeted CF panels used for second- or third-tier molecular CF testing. Conclusions Our use of full gene sequencing as a second-tier CF test in a non-Caucasian patient avoided the problems of missed diagnosis from using Caucasian-biased targeted CF panels currently recommended for second-tier testing. Full gene sequencing should be considered as the standard methodology of second-tier CF testing to enable equal opportunity for CF diagnosis in non-Caucasians.
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Affiliation(s)
- Bennett O V Shum
- Preventive Health Division, Genepath, 302B 7 Help St, Chatswood, NSW, Australia. .,EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
| | - Glenn Bennett
- Preventive Health Division, Genepath, 302B 7 Help St, Chatswood, NSW, Australia
| | | | - R Kishore Kumar
- Cloudnine Hospitals, 1533, 3rd Block, Jayanagar, Bengaluru, Karnataka, India
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Shi R, Wang X, Lu X, Zhu Z, Xu Q, Wang H, Song L, Zhu C. A systematic review of the clinical and genetic characteristics of Chinese patients with cystic fibrosis. Pediatr Pulmonol 2020; 55:3005-3011. [PMID: 32716133 DOI: 10.1002/ppul.24980] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 07/20/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To investigate and summarize the clinical and genetic characteristics of Chinese cystic fibrosis (CF) patients to improve clinicians' understanding and decrease the rates of misdiagnosis and missed diagnoses in China. METHODS The EMBASE, Cochrane Library, PubMed and SinoMed databases were searched for studies involving Chinese CF patients from January 1975 to August 2019. RESULTS In total, 113 Chinese patients, including 53 males and 60 females, were reported. Nineteen patients had a family history of CF. The median age at diagnosis was 8.7 years. Among Chinese CF patients, 70.8% had bronchiectasis, 9.7% had a hemoptysis history, 33.6% had clubbed fingers, 17.7% had allergic bronchopulmonary aspergillosis, and 29.2% had chronic diarrhea; the incidence of malnutrition was 52.2%. Five patients had jaundice, 26 patients had hepatomegaly, and 9 patients had meconium ileus in the neonatal period, and the incidence of liver cirrhosis was 5.3%. The predominant organism in airways was Pseudomonas aeruginosa, followed by Staphylococcus aureus. Seventy-nine patients underwent the sweat test, and all of them were positive, with an average chloride ion level of 122.2 mmol/L. Eighty-eight Chinese CF patients underwent genetic testing, and 74 CF transmembrane conductance regulator (CFTR) gene mutations were reported. The most common gene mutation was c.2909G→A. One Phe508del gene mutation was observed. CONCLUSION The common clinical manifestations and CFTR gene mutations in Chinese CF patients are different from those in Caucasian patients. The age at CF diagnosis in China is relatively old, suggesting that the CF incidence in China may be seriously underestimated.
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Affiliation(s)
- Ruihe Shi
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiufang Wang
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaojing Lu
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhijie Zhu
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qingrong Xu
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haoran Wang
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Song
- Division of Pulmonology, Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Changlian Zhu
- Department of Neonatology, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
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Easteal S, Arkell RM, Balboa RF, Bellingham SA, Brown AD, Calma T, Cook MC, Davis M, Dawkins HJS, Dinger ME, Dobbie MS, Farlow A, Gwynne KG, Hermes A, Hoy WE, Jenkins MR, Jiang SH, Kaplan W, Leslie S, Llamas B, Mann GJ, McMorran BJ, McWhirter RE, Meldrum CJ, Nagaraj SH, Newman SJ, Nunn JS, Ormond-Parker L, Orr NJ, Paliwal D, Patel HR, Pearson G, Pratt GR, Rambaldini B, Russell LW, Savarirayan R, Silcocks M, Skinner JC, Souilmi Y, Vinuesa CG, Baynam G. Equitable Expanded Carrier Screening Needs Indigenous Clinical and Population Genomic Data. Am J Hum Genet 2020; 107:175-182. [PMID: 32763188 PMCID: PMC7413856 DOI: 10.1016/j.ajhg.2020.06.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.
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Affiliation(s)
- Simon Easteal
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia.
| | - Ruth M Arkell
- John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Renzo F Balboa
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia
| | - Shayne A Bellingham
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia
| | - Alex D Brown
- Aboriginal Health Equity, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
| | - Tom Calma
- Poche Centre for Indigenous Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Matthew C Cook
- Department of Immunology, Canberra Hospital, Canberra, ACT 2606, Australia
| | - Megan Davis
- UNSW Law, University of New South Wales, Sydney, NSW 2052, Australia
| | - Hugh J S Dawkins
- HBF Health Limited, Perth, WA 6000, Australia; School of Medicine, The University of Notre Dame Australia, Sydney, NSW 2010, Australia; Sir Walter Murdoch School of Policy and International Affairs, Murdoch University, Murdoch, WA 6150, Australia; Division of Genetics, School of Biomedical Sciences, University of Western Australia, Nedlands, WA 6008, Australia; Centre for Population Health Research, Curtin University of Technology, Bentley, WA 6102, Australia
| | - Marcel E Dinger
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
| | - Michael S Dobbie
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Ashley Farlow
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; Melbourne Integrative Genomics, University of Melbourne, Melbourne, VIC 3010, Australia
| | - Kylie G Gwynne
- Poche Centre for Indigenous Health, University of Sydney, Sydney, NSW 2006, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2113, Australia
| | - Azure Hermes
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia
| | - Wendy E Hoy
- Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
| | - Misty R Jenkins
- Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; La Trobe Institute of Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
| | - Simon H Jiang
- Department of Immunology, Canberra Hospital, Canberra, ACT 2606, Australia
| | - Warren Kaplan
- Informatics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
| | - Stephen Leslie
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; Melbourne Integrative Genomics, University of Melbourne, Melbourne, VIC 3010, Australia
| | - Bastien Llamas
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; Centre of Excellence in Australian Biodiversity and Heritage, School of Biological Sciences, The Environment Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Graham J Mann
- John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Brendan J McMorran
- John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Rebekah E McWhirter
- Centre for Law and Genetics, Faculty of Law, University of Tasmania, Hobart, TAS 7001, Australia
| | | | - Shivashankar H Nagaraj
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000, Australia
| | - Saul J Newman
- Biological Data Science Institute, Australian National University, Canberra, ACT 2600, Australia
| | - Jack S Nunn
- Public Health, La Trobe University, Melbourne, VIC 3086, Australia
| | - Lyndon Ormond-Parker
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC 3010, Australia
| | - Neil J Orr
- Poche Centre for Indigenous Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Devashi Paliwal
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Hardip R Patel
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia
| | - Glenn Pearson
- Aboriginal Health, Telethon Kids Institute, Perth, WA 6009, Australia
| | - Greg R Pratt
- Aboriginal and Torres Strait Islander Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
| | - Boe Rambaldini
- Poche Centre for Indigenous Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Lynette W Russell
- Centre of Excellence in Australian Biodiversity and Heritage, Monash Indigenous Studies Centre, Monash University, Melbourne, VIC 3800, Australia
| | - Ravi Savarirayan
- Victorian Clinical Genetic Services, Murdoch Children's Research Institute, and University of Melbourne, Parkville, VIC 3052, Australia
| | - Matthew Silcocks
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; Melbourne Integrative Genomics, University of Melbourne, Melbourne, VIC 3010, Australia
| | - John C Skinner
- Poche Centre for Indigenous Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Yassine Souilmi
- National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia; School of Biological Sciences, The Environment Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Carola G Vinuesa
- John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia
| | - Gareth Baynam
- Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA 6004, Australia; The Western Australian Register of Developmental Anomalies, Department of Health, Government of Western Australia, Perth, WA 6004, Australia; School of Medicine, Division of Paediatrics and Telethon Kids Institute, University of Western Australia, Perth, WA 6009, Australia.
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11
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Shao H, Hua J, Wu Q, Li X, Zhang M, Wang H, Wu J, Xu L, Xie Y, Li L, Chen H. Identification of a Mutation in the Novel Compound Heterozygous CFTR in a Chinese Family with Cystic Fibrosis. Can Respir J 2020; 2020:6507583. [PMID: 32454915 PMCID: PMC7229557 DOI: 10.1155/2020/6507583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 03/05/2020] [Accepted: 03/13/2020] [Indexed: 02/05/2023] Open
Abstract
Cystic fibrosis (CF) is one of the most common autosomal recessive disorders among Caucasians of Northern European descent but is uncommon in the Chinese population. Objectives. To elucidate the mutation in the novel compound heterozygous CFTR causing CF in Chinese family. Materials and Methods. Clinical samples were obtained from a Chinese family, the brother and sister with recurrent airway infections, hypoxemia and obstructive ventilatory impairment, sinusitis, clubbed fingers, salty sweat, and nasal polyposis. We performed whole-exome sequencing on the family and validated all potential variants by Sanger sequencing. Results. Next-generation sequencing showed a novel compound heterozygous CFTR mutation (c.400 A > G p.Arg134Gly and c.3484 C > T p.Arg1162 ∗ ) which resulted in CF in the family. Conclusions. As this mutation is consistent with the observed clinical manifestations of CF and no other mutations were detected after scanning the gene sequence, we suggest that their CF phenotypes are caused by the compound heterozygous mutation, c.400 A > G p.Arg134Gly and c.3484 C > T p.Arg1162 ∗ . As c.400 A > G is not currently listed in the Cystic Fibrosis Mutation Database, this information, regarding the CF-causing mutations in two Chinese patients, is of interest.
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Affiliation(s)
- Hongxia Shao
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China
| | - Jingna Hua
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China
| | - Qi Wu
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China
| | - Xiaoge Li
- Tianjin Jinnan Xiaozhan Hospital, Tianjin 300353, China
| | - Ming Zhang
- Department of Medical Ultrasonics, Haihe Hospital, Tianjin University, Tianjin 300350, China
| | - Herong Wang
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
| | - Junping Wu
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China
- Department of Tuberculosis Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
| | - Long Xu
- Department of Science and Education, Haihe Hospital, Tianjin University, Tianjin 300350, China
| | - Yi Xie
- Department of Science and Education, Haihe Hospital, Tianjin University, Tianjin 300350, China
| | - Li Li
- Department of Respiratory Medicine, Haihe Hospital, Tianjin University, Tianjin 300350, China
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
| | - Huaiyong Chen
- Tianjin Institute of Respiratory Diseases, Tianjin 300350, China
- Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin 300350, China
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12
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Cabrini G. Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure. Mol Diagn Ther 2019; 23:263-279. [PMID: 30478715 DOI: 10.1007/s40291-018-0372-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Cystic fibrosis (CF), a life-threatening multiorgan genetic disease, is facing a new era of research and development using innovative gene-directed personalized therapies. The priority organ to cure is the lung, which suffers recurrent and chronic bacterial infection and inflammation since infancy, representing the main cause of morbidity and precocious mortality of these individuals. After the disappointing failure of gene-replacement approaches using gene therapy vectors, no single drug is presently available to repair all the CF gene defects. The impressive number of different CF gene mutations is now tackled with different chemical and biotechnological tools tailored to the specific molecular derangements, thanks to the extensive knowledge acquired over many years on the mechanisms of CF cell and organ pathology. This review provides an overview and recalls both the successes and limitations of the different experimental approaches, such as high-throughput screening on chemical libraries to discover CF gene correctors and potentiators, dual-acting compounds, read-through molecules, splicing defect repairing tools, cystic fibrosis transmembrane conductance regulator (CFTR) "amplifiers," CFTR interactome modulators and the first gene editing attempts.
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Affiliation(s)
- Giulio Cabrini
- Laboratory of Molecular Pathology, University Hospital, Verona, Italy. .,Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
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13
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Wang YQ, Hao CL, Jiang WJ, Lu YH, Sun HQ, Gao CY, Wu M. c.753_754delAG, a novel CFTR mutation found in a Chinese patient with cystic fibrosis: A case report and review of the literature. World J Clin Cases 2019; 7:2110-2119. [PMID: 31423445 PMCID: PMC6695543 DOI: 10.12998/wjcc.v7.i15.2110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/23/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cystic fibrosis (CF) is rare in Asian populations relative to the Caucasian population. In this paper, we report the cystic fibrosis transmembrane conductance regulator (CFTR) variation in a family of Chinese CF patients, and systematically review the previous literature.
CASE SUMMARY Here we report a 30-month-old Chinese girl who was diagnosed with CF based on her history and symptoms such as recurrent productive cough, wheezing with repeated infection of Pseudomonas aeruginosa, and parasinusitis. Chest computed tomography (CT) scanning revealed obvious exudative lesions and bilateral bronchiectasis. Liver CT scanning revealed a low-density lesion in the left lobe of the liver. A diagnosis of CF was made based upon CFTR gene tests. The CFTR gene was sequenced using the blood samples of her and her parents and showed a heterozygous novel missense mutation of c.753_754delAG in exon 7. In addition, a heterozygous c.1240 C>T mutation was found in exon 10 of the CFTR. The mutation c.753_754delAG was verified to have been inherited from her mother, and the c.1240 C>T mutation was from her father who was diagnosed with congenital absence of vas deferens.
CONCLUSION A novel mutation of CFTR, c.753_754delAG, was found in a Chinese CF child. c.2909G>A is the most common mutation among Chinese CF patients.
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Affiliation(s)
- Yu-Qing Wang
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Chuang-Li Hao
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Wu-Jun Jiang
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Yan-Hong Lu
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Hui-Quan Sun
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Chun-Yan Gao
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Min Wu
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
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14
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Yuan P, Liang ZK, Liang H, Zheng LY, Li D, Li J, Zhang J, Tian J, Lai LH, Zhang K, He ZY, Zhang QX, Wang WJ. Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing
CFTR
and
ADGRG
2
alleles. Andrology 2019; 7:329-340. [PMID: 30811104 DOI: 10.1111/andr.12592] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 12/06/2018] [Accepted: 01/08/2019] [Indexed: 12/12/2022]
Affiliation(s)
- P. Yuan
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - Z. K. Liang
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - H. Liang
- BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable Species Peking‐Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, and Center for Quantitative Biology Peking University Beijing China
| | - L. Y. Zheng
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - D. Li
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - J. Li
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - J. Zhang
- Reproductive Medicine Center Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou China
| | - J. Tian
- Ultrasonography Department Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - L. H. Lai
- BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable Species Peking‐Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, and Center for Quantitative Biology Peking University Beijing China
| | - K. Zhang
- State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou China
| | - Z. Y. He
- State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou China
| | - Q. X. Zhang
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
| | - W. J. Wang
- IVF Center Department of Obstetrics and Gynecology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China
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15
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Li H, Lin L, Hu X, Li C, Zhang H. Liver Failure in a Chinese Cystic Fibrosis Child With Homozygous R553X Mutation. Front Pediatr 2019; 7:36. [PMID: 30842938 PMCID: PMC6391319 DOI: 10.3389/fped.2019.00036] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 01/28/2019] [Indexed: 12/25/2022] Open
Abstract
Cystic fibrosis (CF) is a relatively rare disease in Asians with various clinical characteristics, including CF-associated liver disease (CFLD), which is a common early non-pulmonary complication. This case report describes a Chinese CF patient harboring a homozygous nonsense mutation (c.1657C>T, p.R553X) who was failure to thrive and had intermittently diarrhea during the first year after birth. Liver function test of the patient showed the mildly and intermittently elevated alanine aminotransferase (ALT) levels ranging from 70 to 92 U/L and aspartate aminotransferase (AST) levels ranging from 80 to 90 U/L, which began at 8 months of age and lasted for 4 years without CF diagnosis. In addition, abdominal computed tomography (CT) revealed diffuse fatty infiltration of the liver at 4 years old and gradually developed hepatic cirrhosis. Subsequently, cirrhosis rapidly progressed with obvious splenomegaly and pancreatic insufficiency and the patient died of liver failure with coagulopathy by the age of 6 years old. Pediatricians should remain vigilant to avoid failure to diagnose CF, the occurrence of which may be underestimated, and pay greater attention to the patients with atypical clinical manifestations in Asian countries.
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Affiliation(s)
- Haiyan Li
- Department of Pediatric Pulmonology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Li Lin
- Department of Pediatric Pulmonology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaoguang Hu
- Department of Pediatric Pulmonology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Changchong Li
- Department of Pediatric Pulmonology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hailin Zhang
- Department of Pediatric Pulmonology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
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16
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Guo X, Liu K, Liu Y, Situ Y, Tian X, Xu KF, Zhang X. Clinical and genetic characteristics of cystic fibrosis in CHINESE patients: a systemic review of reported cases. Orphanet J Rare Dis 2018; 13:224. [PMID: 30558651 PMCID: PMC6296146 DOI: 10.1186/s13023-018-0968-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 12/04/2018] [Indexed: 02/07/2023] Open
Abstract
Cystic fibrosis (CF) is a rare disease most commonly seen in Caucasians. Only a few Chinese CF patients have been described in literature, taking into account the large population of China. In this systematic review, we collected the clinical and genetic information of 71 Chinese CF patients based on all available data. Compared with Caucasians, Chinese CF patients often present atypical symptoms, mainly displaying symptoms of pulmonary infection with fewer digestive symptoms. An ethnicity-specific CFTR variant spectrum was also observed in CF patients of Chinese origin, with p.Gly970Asp as the most common mutation while p.Phe508del, the most common pathogenic mutation in CF patients of Caucasian origin, is rare, suggesting the necessity of a Chinese-specific CFTR variant screening panel. Besides, multiplex ligation-dependent probe amplification analysis should be routinely considered, especially for those with unidentified mutations. Potential under-diagnosis of CF in Chinese patients might be caused by a combination of atypical clinical features and genetic heterogeneity in Chinese CF patients, the inaccessibility of sweat and genetic testing facilities, and the one-child policy in China. With the approval of promising small molecule correctors and potentiators, molecular characterization of Chinese-specific CFTR mutations will help to realize more precise treatment for Chinese CF patients.
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Affiliation(s)
- Xiaobei Guo
- Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.,Emergency Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Keqiang Liu
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China
| | - Yaping Liu
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
| | - Yusen Situ
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Xinlun Tian
- Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.
| | - Kai-Feng Xu
- Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Xue Zhang
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China
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17
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Xu S, Zhong W, Shen Z, Dai C, Xia H, Guan Q, Bai L, Yu J. Analysis of the clinical outcomes of fetal bowel dilatation combined with other abnormal ultrasonographic features. J Matern Fetal Neonatal Med 2017; 32:992-996. [DOI: 10.1080/14767058.2017.1397123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Suting Xu
- Department of Gynecological Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Wei Zhong
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Zhuanxing Shen
- Department of Gynecological Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Changping Dai
- Department of Ultrasound, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Huimin Xia
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Qiansi Guan
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Lihua Bai
- Department of Ultrasound, Guangzhou Women and Children’s Medical Center, Guangzhou, China
| | - Jiakang Yu
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China
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18
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Xu J, Yin Y, Zhang L, Zhang J, Yuan S, Zhang H. Four case reports of Chinese cystic fibrosis patients and literature review. Pediatr Pulmonol 2017; 52:1020-1028. [PMID: 28608624 DOI: 10.1002/ppul.23744] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Accepted: 05/07/2017] [Indexed: 12/22/2022]
Abstract
AIM Cystic fibrosis (CF) is an extremely rare disease in Asians. Here, we report four Chinese children with CF and review the literature about Chinese CF patients. METHODS The cystic fibrosis transmembrane conductance regulator (CFTR) gene testing was performed on four suspected patients for CF screening. We also reviewed the literature about Chinese CF patients from 1970s. The clinical data of all these CF patients were summarized. RESULTS We diagnosed four CF patients who had mutations in the CFTR gene. We identified six different mutations in the four patients. The c.1766+5G>T, c.595C>T, c.2909G>A, and c.4056G>C had been reported already. The two splicing mutations of c.579+1_579+2insACAT and c.1117-1G>C were novel mutations. There have been 46 Chinese CF patients reported in literature from 1974 up to present (2016.12). The clinical manifestations of CF involved several systems. The most common symptom was recurrent pulmonary infections. Thirty-three different mutations were identified; c.1766 + 5G>T was the most common mutation among Chinese CF patients. Only one of these mutations (R553X) was in the Caucasian CF screening panel. The spectrum of CFTR mutations in Chinese was highly different from that of Caucasian. CONCLUSIONS There was a high risk of misdiagnosis or delayed diagnosis of CF even in suspected cases in China. It is necessary to educate Chinese clinicians about the signs, symptoms, and diagnosis of cystic fibrosis and promote the implementation of the sweat chloride test.
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Affiliation(s)
- Juan Xu
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
| | - Yong Yin
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
| | - Lei Zhang
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
| | - Jing Zhang
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
| | - Shuhua Yuan
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
| | - Hao Zhang
- Department of Respiratory Medicine, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University of Medicine, Pudong, Shanghai, China
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