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Huang C, Chu LM, Liang B, Wu HL, Li BS, Ren S, Hou ML, Nie HC, Kong LY, Fan LQ, Du J, Zhu WB. Comparative genetic analysis of blood and semen samples in sperm donors from Hunan, China. Ann Med 2025; 57:2447421. [PMID: 39757988 PMCID: PMC11721621 DOI: 10.1080/07853890.2024.2447421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/17/2024] [Accepted: 11/22/2024] [Indexed: 01/07/2025] Open
Abstract
OBJECTIVES At present, most genetic tests or carrier screening are performed with blood samples, and the known carrier rate of disease-causing variants is also derived from blood. For semen donors, what is really passed on to offspring is the pathogenic variant in their sperm. This study aimed to determine whether pathogenic variants identified in the sperm of young semen donors are also present in their blood, and whether matching results for blood are consistent with results for sperm. METHODS We included 40 paired sperm and blood samples from 40 qualified semen donors at the Hunan Province Human Sperm Bank of China. All samples underwent exome sequencing (ES) analysis, and the pathogenicity was assessed according to the American College of Medical Genetics (ACMG) guidelines. Scoring for sperm donation matching, which was based on gene scoring and variant scoring, was also used to assess the consistency of sperm and blood genetic test results. RESULTS A total of 108 pathogenic (P)/likely pathogenic (LP) variants in 82 genes were identified. The highest carrier had 7 variants, and there was also one donor did not carry any P/LP variant. On average, each donor carried 2.7 P/LP variants. Among all the P/LP variants, missense mutation was the dominant type and most of them were located in exonic regions. Chromosome 1 harboured the largest number of variants and no pathogenic copy number variants (CNV) was identified in semen donors. The P/LP variant of all the 40 semen donors was consistent by comparing sperm and blood. Except for one case that was slightly different, the rest simulated matching results for blood were all consistent with results for sperm. CONCLUSIONS It is reasonable to choose either blood or sperm for genetic screening in semen donors.
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Affiliation(s)
- Chuan Huang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Li-Ming Chu
- Basecare Medical Device Co., Ltd, Suzhou, China
| | - Bo Liang
- State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Hui-Lan Wu
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
| | - Bai-Shun Li
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
| | - Shuai Ren
- Basecare Medical Device Co., Ltd, Suzhou, China
| | | | - Hong-Chuan Nie
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
| | | | - Li-Qing Fan
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Juan Du
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wen-Bing Zhu
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of International Trust and Investment Corporation (CITIC)-Xiangya, Changsha, China
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China
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Aboagye ET, Adadey SM, Esoh K, Jonas M, de Kock C, Amenga-Etego L, Awandare GA, Wonkam A. Age Estimate of GJB2-p.(Arg143Trp) Founder Variant in Hearing Impairment in Ghana, Suggests Multiple Independent Origins across Populations. BIOLOGY 2022; 11:476. [PMID: 35336849 PMCID: PMC8945073 DOI: 10.3390/biology11030476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/15/2022] [Accepted: 03/17/2022] [Indexed: 12/29/2022]
Abstract
Gap junction protein beta 2 (GJB2) (connexin 26) variants are commonly implicated in non-syndromic hearing impairment (NSHI). In Ghana, the GJB2 variant p.(Arg143Trp) is the largest contributor to NSHI and has a reported prevalence of 25.9% in affected multiplex families. To date, in the African continent, GJB2-p.(Arg143Trp) has only been reported in Ghana. Using whole-exome sequencing data from 32 individuals from 16 families segregating NSHI, and 38 unrelated hearing controls with the same ethnolinguistic background, we investigated the date and origin of p.(Arg143Trp) in Ghana using linked markers. With a Bayesian linkage disequilibrium gene mapping method, we estimated GJB2-p.(Arg143Trp) to have originated about 9625 years (385 generations) ago in Ghana. A haplotype analysis comparing data extracted from Ghanaians and those from the 1000 Genomes project revealed that GJB2-p.(Arg143Trp) is carried on different haplotype backgrounds in Ghanaian and Japanese populations, as well as among populations of European ancestry, lending further support to the multiple independent origins of the variant. In addition, we found substantial haplotype conservation in the genetic background of Ghanaian individuals with biallelic GJB2-p.(Arg143Trp) compared to the GJB2-p.(Arg143Trp)-negative group with normal hearing from Ghana, suggesting a strong evolutionary constraint in this genomic region in Ghanaian populations that are homozygous for GJB2-p.(Arg143Trp). The present study evaluates the age of GJB2-p.(Arg143Trp) at 9625 years and supports the multiple independent origins of this variant in the global population.
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Affiliation(s)
- Elvis Twumasi Aboagye
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; (E.T.A.); (S.M.A.); (L.A.-E.); (G.A.A.)
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
| | - Samuel Mawuli Adadey
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; (E.T.A.); (S.M.A.); (L.A.-E.); (G.A.A.)
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
| | - Kevin Esoh
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
| | - Mario Jonas
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
| | - Carmen de Kock
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
| | - Lucas Amenga-Etego
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; (E.T.A.); (S.M.A.); (L.A.-E.); (G.A.A.)
| | - Gordon A. Awandare
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; (E.T.A.); (S.M.A.); (L.A.-E.); (G.A.A.)
| | - Ambroise Wonkam
- Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (K.E.); (M.J.); (C.d.K.)
- McKusick-Nathans Institute and Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Zhao LJ, Zhang ZL, Fu Y. Novel m.4268T>C mutation in the mitochondrial tRNA Ile gene is associated with hearing loss in two Chinese families. World J Clin Cases 2022; 10:205-216. [PMID: 35071519 PMCID: PMC8727281 DOI: 10.12998/wjcc.v10.i1.205] [Citation(s) in RCA: 1] [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: 06/17/2021] [Revised: 07/23/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Herein, we report the genetic, clinical, molecular and biochemical features of two Han Chinese pedigrees with suggested maternally transmitted non-syndromic hearing loss.
AIM To investigate the pathophysiology of hearing loss associated with mitochondrial tRNA mutations.
METHODS Sixteen subjects from two Chinese families with hearing loss underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included the measurements of tRNA levels using lymphoblastoid cell lines derived from five affected matrilineal relatives of these families and three control subjects.
RESULTS Three of the 16 matrilineal relatives in these families exhibited a variable seriousness and age-at-onset (8 years) of deafness. Analysis of mtDNA mutation identified the novel homoplasmic tRNAIle 4268T>C mutation in two families both belonging to haplogroup D4j. The 4268T>C mutation is located in a highly conserved base pairing (6U–67A) of tRNAIle. The elimination of 6U–67A base-pairing may change the tRNAIle metabolism. Functional mutation was supported by an approximately 64.6% reduction in the level of tRNAIle observed in the lymphoblastoid cell lines with the 4268T>C mutation, in contrast to the wild-type cell lines. The reduced level of tRNA was below the proposed threshold for normal respiration in lymphoblastoid cells. However, genotyping analysis did not detect any mutations in the prominent deafness-causing gene GJB2 in any members of the family.
CONCLUSION These data show that the novel tRNAIle 4268T>C mutation was involved in maternally transmitted deafness. However, epigenetic, other genetic, or environmental factors may be attributed to the phenotypic variability. These findings will be useful for understanding families with maternally inherited deafness.
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Affiliation(s)
- Li-Jing Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Zhi-Li Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Yong Fu
- Department of Otorhinolaryngology Head and Neck Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
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Wang H, Gao Y, Guan J, Lan L, Yang J, Xiong W, Zhao C, Xie L, Yu L, Wang D, Wang Q. Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation. Front Cell Dev Biol 2021; 9:647240. [PMID: 33718389 PMCID: PMC7953049 DOI: 10.3389/fcell.2021.647240] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 02/08/2021] [Indexed: 01/01/2023] Open
Abstract
Objective To report the phenotypic heterogeneity of GJB2 c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes. Methods Mutation screening of GJB2 was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase–quantitative PCR was conducted to test the expression of Connexin30. Results We identified a Chinese autosomal recessive hearing loss family with the GJB2 c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified. Conclusion Post-lingual and/or moderate hearing impairment phenotypes of GJB2 c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of GJB2 pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.
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Affiliation(s)
- Hongyang Wang
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yun Gao
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Jing Guan
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Lan Lan
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Ju Yang
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Wenping Xiong
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Cui Zhao
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Linyi Xie
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Lan Yu
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Dayong Wang
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
| | - Qiuju Wang
- College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.,National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.,Key Lab of Hearing Impairment Science of Ministry of Education, Beijing, China.,Key Lab of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China
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5
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High Rates of Three Common GJB2 Mutations c.516G>C, c.-23+1G>A, c.235delC in Deaf Patients from Southern Siberia Are Due to the Founder Effect. Genes (Basel) 2020; 11:genes11070833. [PMID: 32708339 PMCID: PMC7397271 DOI: 10.3390/genes11070833] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/10/2020] [Accepted: 07/17/2020] [Indexed: 11/17/2022] Open
Abstract
The mutations in the GJB2 gene (13q12.11, MIM 121011) encoding transmembrane protein connexin 26 (Cx26) account for a significant portion of hereditary hearing loss worldwide. Earlier we found a high prevalence of recessive GJB2 mutations c.516G>C, c.-23+1G>A, c.235delC in indigenous Turkic-speaking Siberian peoples (Tuvinians and Altaians) from the Tyva Republic and Altai Republic (Southern Siberia, Russia) and proposed the founder effect as a cause for their high rates in these populations. To reconstruct the haplotypes associated with each of these mutations, the genotyping of polymorphic genetic markers both within and flanking the GJB2 gene was performed in 28 unrelated individuals homozygous for c.516G>C (n = 18), c.-23+1G>A (n = 6), or c.235delC (n = 4) as well as in the ethnically matched controls (62 Tuvinians and 55 Altaians) without these mutations. The common haplotypes specific for mutations c.516G>C, c.-23+1G>A, or c.235delC were revealed implying a single origin of each of these mutations. The age of mutations estimated by the DMLE+ v2.3 software and the single marker method is discussed in relation to ethnic history of Tuvinians and Altaians. The data obtained in this study support a crucial role of the founder effect in the high prevalence of GJB2 mutations c.516G>C, c.-23+1G>A, c.235delC in indigenous populations of Southern Siberia.
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Chakchouk I, Zhang D, Zhang Z, Francioli LC, Santos-Cortez RLP, Schrauwen I, Leal SM. Disparities in discovery of pathogenic variants for autosomal recessive non-syndromic hearing impairment by ancestry. Eur J Hum Genet 2019; 27:1456-1465. [PMID: 31053783 PMCID: PMC6777454 DOI: 10.1038/s41431-019-0417-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 04/01/2019] [Accepted: 04/16/2019] [Indexed: 12/22/2022] Open
Abstract
Hearing impairment (HI) is characterized by extensive genetic heterogeneity. To determine the population-specific contribution of known autosomal recessive nonsyndromic (ARNS)HI genes and variants to HI etiology; pathogenic and likely pathogenic (PLP) ARNSHI variants were selected from ClinVar and the Deafness Variation Database and their frequencies were obtained from gnomAD for seven populations. ARNSHI prevalence due to PLP variants varies greatly by population ranging from 96.9 affected per 100,000 individuals for Ashkenazi Jews to 5.2 affected per 100,000 individuals for Africans/African Americans. For Europeans, Finns have the lowest prevalence due to ARNSHI PLP variants with 9.5 affected per 100,000 individuals. For East Asians, Latinos, non-Finish Europeans, and South Asians, ARNSHI prevalence due to PLP variants ranges from 17.1 to 33.7 affected per 100,000 individuals. ARNSHI variants that were previously reported in a single ancestry or family were observed in additional populations, e.g., USH1C p.(Q723*) reported in a Chinese family was the most prevalent pathogenic variant observed in gnomAD for African/African Americans. Variability between populations is due to how extensively ARNSHI has been studied, ARNSHI prevalence and ancestry specific ARNSHI variant architecture which is impacted by population history. Our study demonstrates that additional gene and variant discovery studies are necessary for all populations and particularly for individuals of African ancestry.
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Affiliation(s)
- Imen Chakchouk
- Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
| | - Di Zhang
- Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
| | - Zhihui Zhang
- Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA
| | - Laurent C Francioli
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
| | | | - Isabelle Schrauwen
- Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA
| | - Suzanne M Leal
- Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
- Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
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Posukh OL, Zytsar MV, Bady-Khoo MS, Danilchenko VY, Maslova EA, Barashkov NA, Bondar AA, Morozov IV, Maximov VN, Voevoda MI. Unique Mutational Spectrum of the GJB2 Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys). Genes (Basel) 2019; 10:E429. [PMID: 31195736 PMCID: PMC6627114 DOI: 10.3390/genes10060429] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 05/30/2019] [Accepted: 06/03/2019] [Indexed: 01/09/2023] Open
Abstract
Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians-an indigenous population of the Tyva Republic (Southern Siberia, Russia). Sanger sequencing was applied to analysis of coding (exon 2) and non-coding regions of GJB2 in a cohort of Tuvinian patients with hearing impairments (n = 220) and ethnically matched controls (n = 157). Diagnosis of DFNB1A was established for 22.3% patients (28.8% of familial vs 18.6% of sporadic cases). Our results support that patients with monoallelic GJB2 mutations (8.2%) are coincidental carriers. Recessive mutations p.Trp172Cys, c.-23+1G>A, c.235delC, c.299_300delAT, p.Val37Ile and several benign variants were found in examined patients. A striking finding was a high prevalence of rare variant p.Trp172Cys (c.516G>C) in Tuvinians accounting for 62.9% of all mutant GJB2 alleles and a carrier frequency of 3.8% in controls. All obtained data provide important targeted information for genetic counseling of affected Tuvinian families and enrich current information on variability of GJB2 worldwide.
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Affiliation(s)
- Olga L Posukh
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
- Novosibirsk State University, 630090 Novosibirsk, Russia.
| | - Marina V Zytsar
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
| | - Marita S Bady-Khoo
- Research Institute of Medical-Social Problems and Management of the Republic of Tyva, 667000 Kyzyl, Russia.
- Perinatal Center of the Republic of Tyva, 667000 Kyzyl, Russia.
| | - Valeria Yu Danilchenko
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
| | - Ekaterina A Maslova
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
- Novosibirsk State University, 630090 Novosibirsk, Russia.
| | - Nikolay A Barashkov
- Yakut Scientific Centre of Complex Medical Problems, 677019 Yakutsk, Russia.
- M.K. Ammosov North-Eastern Federal University, 677027 Yakutsk, Russia.
| | - Alexander A Bondar
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
| | - Igor V Morozov
- Novosibirsk State University, 630090 Novosibirsk, Russia.
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
| | - Vladimir N Maximov
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
- Novosibirsk State University, 630090 Novosibirsk, Russia.
| | - Michael I Voevoda
- Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
- Novosibirsk State University, 630090 Novosibirsk, Russia.
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8
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Huang B, Han M, Wang G, Huang S, Zeng J, Yuan Y, Dai P. Genetic mutations in non-syndromic deafness patients in Hainan Province have a different mutational spectrum compared to patients from Mainland China. Int J Pediatr Otorhinolaryngol 2018; 108:49-54. [PMID: 29605365 DOI: 10.1016/j.ijporl.2018.02.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 01/18/2018] [Accepted: 02/11/2018] [Indexed: 10/18/2022]
Abstract
OBJECTIVES To provide appropriate genetic testing and counseling for non-syndromic hearing impairment patients in Hainan Province, an island in the South China Sea. METHODS 299 unrelated students with non-syndromic hearing loss who attended a special education school in Hainan Province were enrolled in this study. Three prominent deafness-related genes (GJB2, SLC26A4, and mtDNA 12S rRNA) were analyzed using Sanger sequencing. RESULTS GJB2 mutations were detected in 32.78% (98/299) of the entire cohort; however, only 5.69% (17/299) had two confirmed pathogenic mutations. The most common mutation observed in this population was c.109G > A in the GJB2 gene, with an allelic frequency of 15.05% (90/598), which is significantly higher than that reported in previous cohorts. A total of 16 patients had two confirmed pathogenic SLC26A4 gene mutations, and 16 patients had one. The IVS7-2A > G mutation was the most commonly observed, with an allelic frequency of 3.51% (21/598). Three patients had a m.1555A > G mutation in the mtDNA 12S rRNA gene. CONCLUSIONS These results reveal that genetic etiology occurred in 11.71% (35/299) of patients, suggesting that Hainan province have a different mutational spectrum compare to Mainland China in non-syndromic deafness patients, which provide useful information to genetic counseling in Hainan province.
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Affiliation(s)
- Bangqing Huang
- Department of Otorhinolaryngology, Hainan Branch of PLA General Hospital, Sanya 572013, PR China
| | - Mingyu Han
- Department of Otorhinolaryngology, Hainan Branch of PLA General Hospital, Sanya 572013, PR China; Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, PR China
| | - Guojian Wang
- Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, PR China
| | - ShaSha Huang
- Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, PR China
| | - Jialing Zeng
- Department of Otorhinolaryngology, Hainan Branch of PLA General Hospital, Sanya 572013, PR China
| | - Yongyi Yuan
- Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, PR China.
| | - Pu Dai
- Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, PR China.
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Large scale newborn deafness genetic screening of 142,417 neonates in Wuhan, China. PLoS One 2018; 13:e0195740. [PMID: 29634755 PMCID: PMC5892933 DOI: 10.1371/journal.pone.0195740] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 03/28/2018] [Indexed: 11/19/2022] Open
Abstract
Almost one third of the three million people in China suffering severe deafness are children, and 50% of these cases are believed to have genetic components to their etiology. Newborn hearing genetic screening can complement Universal Neonatal Hearing Screening for the diagnosis of congenital hearing loss as well as identifying children at risk for late-onset and progressive hearing impairment. The aim of this joint academic and Ministry of Health project was to prototype a cost effective newborn genetic screen in a community health setting on a city-wide level, and to ascertain the prevalence of variation at loci that have been associated with non-syndromic hearing loss. With the participation of 143 local hospitals in the city of Wuhan, China we screened 142,417 neonates born between May 2014 and Dec. 2015. The variants GJB2 c.235delC, SLC26A4 c.919-2A>G, and mitochondrial variants m.1555A>G and m.1494C>T were assayed using real time PCR. Newborns found to carry a variant were re-assayed by sequencing in duplicate. Within a subset of 707 newborns we assayed using real-time PCR and ARMS-PCR to compare cost, sensitivity and operating procedure. The most frequent hearing loss associated allele detected in this population was the 235delC variant in GJB2 gene. In total, 4289 (3.01%) newborns were found to carry at least one allele of either GJB2 c.235delC, SLC26A4 c.919-2A>G or two assayed MT-RNR1 variants. There was complete accordance between the real-time PCR and the ARMS PCR, though the real-time PCR had a much lower failure rate. Real-time PCR had a lower cost and operating time than ARMS PCR. Ongoing collaboration with the participating hospitals will determine the specificity and sensitivity of the association of the variants with hearing loss at birth and arising in early childhood, allowing an estimation of the benefits of newborn hearing genetic screening in a large-scale community setting.
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Yuan EF, Xia W, Huang JT, Hu L, Liao X, Dai X, Liu SM. A sensitive and convenient method for clinical detection of non-syndromic hearing loss-associated common mutations. Gene 2017; 628:322-328. [PMID: 28734895 DOI: 10.1016/j.gene.2017.07.045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 06/21/2017] [Accepted: 07/13/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND The majority of non-syndromic hearing loss (NSHL) patients result from causative mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA genes. Accurate detection of these genetic mutations is increasingly recognized for its clinical significance to reduce incidence and guide individual treatment of NSHL. Current methods for clinical practice are labor intensive, expensive or of low sensitivity. METHODS Genomic DNA from 7 newborns not passing the hearing screening and 94 newborns passing the hearing screening were analyzed for the common mutations using high resolution melting analysis (HRMA) and Sanger sequencing. RESULTS Our newly developed HRMA allowed the hot-spot mutations of GJB2 c.176_191del16 and c.235delC, SLC26A4 IVS7-2A>G and mitochondrial 12S rRNA 1494C>T and 1555A>G to be detected by melting profiles based on small amplicons. HRMA can distinguish different content mutant DNA from wildtype DNA, with a detection limit of 5%. Moreover, the results were highly concordant between HRMA and Sanger sequencing. CONCLUSIONS These results indicate that HRMA could be used as a routine clinical method for prenatal diagnosis and newborn genetic screening due to its accuracy, sensitivity, and rapid, low-cost and less laborious workflows.
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Affiliation(s)
- Er-Feng Yuan
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan 430071, China
| | - Wei Xia
- Department of Clinical Laboratory, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China
| | - Jing-Tao Huang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan 430071, China
| | - Ling Hu
- Department of Neurology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China
| | - Xing Liao
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan 430071, China
| | - Xiang Dai
- Laboratory of Reproductive Medicine, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China
| | - Song-Mei Liu
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan 430071, China.
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Kim SY, Kim AR, Kim NKD, Lee C, Kim MY, Jeon EH, Park WY, Choi BY. Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not? Medicine (Baltimore) 2016; 95:e3029. [PMID: 27057829 PMCID: PMC4998745 DOI: 10.1097/md.0000000000003029] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
The molecular etiology of nonsyndromic sensorineural hearing loss (SNHL) in subjects with only one detectable autosomal recessive GJB2 mutation is unclear. Here, we report GJB2 single heterozygotes with various final genetic diagnoses and suggest appropriate diagnostic strategies. A total of 160 subjects with SNHL without phenotypic markers were screened for GJB2 mutations. Single-nucleotide variants or structural variations within the DFNB1 locus or in other deafness genes were examined by Sanger sequencing, breakpoint PCR, and targeted exome sequencing (TES) of 129 deafness genes. We identified 27 subjects with two mutations and 10 subjects with only one detectable mutation in GJB2. The detection rate of the single GJB2 mutation among the 160 SNHL subjects in the present study (6.25%) was higher than 2.58% in normal hearing controls in Korean. The DFNB1 was clearly excluded as a molecular etiology in four (40%) subjects: other recessive deafness genes (N = 3) accounted for SNHL and the causative gene for the other non-DFNB1 subject (N = 1) was not identified. The etiology of additional two subjects was potentially explained by digenic etiology (N = 2) of GJB2 with MITF and GJB3, respectively. The contribution of the single GJB2 mutation in the four remaining subjects is unclear. Comprehensive diagnostic testing including TES is prerequisite for understanding GJB2 single heterozygotes.
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Affiliation(s)
- So Young Kim
- From the Department of Otorhinolaryngology-Head and Neck Surgery, CHA medical center, CHA university, Seongnam (SYK), Department of Otorhinolaryngology-Head and Neck Surgery (SYK, ARK), Seoul National University Hospital, Seoul National University College of Medicine; Samsung Genome Institue (NKDK, CL), Samsung Medical Center, Seoul, Korea; Department of Health Sciences and Technology (CL), SAIHST, Sungkyunkwan University, Seobu-ro, Jangan-gu, Suwon, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery (MYK, E-HJ, BYC), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam; Samsung Genome Institute (W-YP), Samsung Medical Center; Department of Molecular Cell Biology, School of Medicine (W-YP), Sungkyunkwan University; Sensory Organ Research Institute (BYC), Seoul National University Medical Research Center, Seoul, Korea; and Wide River Institute of Immunology (BYC), Seoul National University College of Medicine, Hongcheon, Republic of Korea
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12
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Tsukada K, Nishio SY, Hattori M, Usami SI. Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a literature review. Ann Otol Rhinol Laryngol 2015; 124 Suppl 1:61S-76S. [PMID: 25999548 DOI: 10.1177/0003489415575060] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE The mutation spectrum of the GJB2 and SLC26A4 genes, the 2 most common genes causing deafness, are known to be ethnic specific. In this study, the spectrum of the reported GJB2 and SLC26A4 mutations in different populations are reviewed and considered from a human migration perspective. METHODS Fifty-two and 17 articles on GJB2 and SLC26A4 mutations, respectively, were reviewed through the PubMed database from April 1996 to September 2014. The 4 most prevalent mutations were selected and compared. A cluster analysis was subsequently performed for these selected mutations. RESULTS The present review of frequent mutations shows the ethnic-specific GJB2 and SLC26A4 gene mutation spectrum. A cluster analysis of the GJB2 and SLC26A4 genes revealed similarities between ethnic populations. CONCLUSION The mutation spectrum reviewed in this study clearly indicated that the frequent mutations in the GJB2 and SLC26A4 genes are consistent with the founder mutation hypothesis. A comparison with the Y-chromosome phylogenetic tree indicated that these mutations may have occurred during human migration.
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Affiliation(s)
- Keita Tsukada
- Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shin-Ya Nishio
- Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan
| | - Mitsuru Hattori
- Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shin-Ichi Usami
- Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan
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Zheng J, Ying Z, Cai Z, Sun D, He Z, Gao Y, Zhang T, Zhu Y, Chen Y, Guan MX. GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss. PLoS One 2015; 10:e0128691. [PMID: 26043044 PMCID: PMC4456361 DOI: 10.1371/journal.pone.0128691] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 04/29/2015] [Indexed: 11/17/2022] Open
Abstract
Mutations in Gap Junction Beta 2 (GJB2) have been reported to be a major cause of non-syndromic hearing loss in many populations worldwide. The spectrums and frequencies of GJB2 variants vary substantially among different ethnic groups, and the genotypes among these populations remain poorly understood. In the present study, we carried out a systematic and extended mutational screening of GJB2 gene in 1067 Han Chinese subjects with non-syndromic hearing loss, and the resultant GJB2 variants were evaluated by phylogenetic, structural and bioinformatic analysis. A total of 25 (23 known and 2 novel) GJB2 variants were identified, including 6 frameshift mutations, 1 nonsense mutation, 16 missense mutations and 2 silent mutations. In this cohort, c.235delC is the most frequently observed pathogenic mutation. The phylogenetic, structural and bioinformatic analysis showed that 2 novel variants c.127G>T (p.V43L), c.293G>C (p.R98P) and 2 known variants c. 107T>C (p.L36P) and c.187G>T (p.V63L) are localized at highly conserved amino acids. In addition, these 4 mutations are absent in 203 healthy individuals, therefore, they are probably the most likely candidate pathogenic mutations. In addition, 66 (24 novel and 42 known) genotypes were identified, including 6 homozygotes, 20 compound heterozygotes, 18 single heterozygotes, 21 genotypes harboring only polymorphism(s) and the wild type genotype. Among these, 153 (14.34%) subjects were homozygous for pathogenic mutations, 63 (5.91%) were compound heterozygotes, and 157 (14.71%) carried single heterozygous mutation. Furthermore, 65.28% (141/216) of these cases with two pathogenic mutations exhibited profound hearing loss. These data suggested that mutations in GJB2 gene are responsible for approximately 34.96% of non-syndromic hearing loss in Han Chinese population from Zhejiang Province in eastern China. In addition, our results also strongly supported the idea that other factors such as alterations in regulatory regions, additional genes, and environmental factors may contribute to the clinical manifestation of deafness.
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Affiliation(s)
- Jing Zheng
- Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhengbiao Ying
- Department of Otolaryngology, Wenling People’s Hospital, Wenzhou Medical University, Taizhou, China
| | - Zhaoyang Cai
- Department of Otolaryngology, Wenling People’s Hospital, Wenzhou Medical University, Taizhou, China
| | - Dongmei Sun
- Department of Laboratory Medicine, Jinhua Municipal Central Hospital, Jinhua, China
| | - Zheyun He
- Attardi Institute of Mitochondrial Biomedicine, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yinglong Gao
- Attardi Institute of Mitochondrial Biomedicine, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ting Zhang
- Department of Otolaryngology, Wenling People’s Hospital, Wenzhou Medical University, Taizhou, China
| | - Yi Zhu
- Department of Otolaryngology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Ye Chen
- Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Min-Xin Guan
- Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
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Xin F, Yuan Y, Deng X, Han M, Wang G, Zhao J, Gao X, Liu J, Yu F, Han D, Dai P. Genetic mutations in nonsyndromic deafness patients of Chinese minority and Han ethnicities in Yunnan, China. J Transl Med 2013; 11:312. [PMID: 24341454 PMCID: PMC3878508 DOI: 10.1186/1479-5876-11-312] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Accepted: 12/11/2013] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Each year in China, 30,000 babies are born with congenital hearing impairment. However, the molecular etiology of hearing impairment in the Yunnan Province population where more than 52 minorities live has not been thoroughly investigated. To provide appropriate genetic testing and counseling to these families, we investigated the molecular etiology of nonsyndromic deafness in this population. METHODS Unrelated students with hearing loss (n = 235) who attended Kunming Huaxia secondary specialized school in Yunnan enrolled in this study. Three prominent deafness-related genes, GJB2, SLC26A4 and mtDNA 12S rRNA, were analyzed. High-resolution temporal bone computed tomography (CT) scan examinations were performed in 100 cases, including 16 cases with SLC26A4 gene variants, and 37 minorities and 47 Han cases without any SLC26A4 gene mutation. RESULTS The GJB2 mutation was detected in 16.67% (7/42) of minority patients and 17.62% (34/193) of Chinese Han patients (P > 0.05). 235delC was the hotspot mutation in nonsyndromic hearing loss (NSHL) patients, whereas 35delG was not found. The 431_450del19 mutation was detected for the first time in Han NSHL patients, which resulted in a premature stop codon and changed the protein. The SLC26A4 mutation was found in 9.52% (4/42) of minority patients and 9.84% (19/193) of Han Chinese patients (P > 0.05). The frequencies of mtDNA 12S rRNA mutation in minority and Han Chinese patients were 11.90% (5/42) and 7.77% (15/193; P > 0.05), respectively. Sixteen (16/23, 69.57%) patients with SLC26A4 mutations received temporal bone CT scan, and 14 patients were diagnosed with enlarged vestibular aqueducts (EVAs); the other 2 patients had normal inner ear development. The ratio of EVA in the minorities was 14.63% (6/41). CONCLUSIONS In this study, a total of 35.74% deaf patients showed evidence of genetic involvement, based on either genetic screening or family history; 17.45%, 9.79%, and 8.51% of the patients were determined to have inherited hearing impairment caused by GJB2, SLC26A4, and mtDNA 1555A > G mutations. There was no significant difference in deafness associated gene mutational spectrum and frequency between the Yunnan minority and Han patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Pu Dai
- Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing 100853, P,R, China.
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