Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Clin Cases. Jul 6, 2026; 14(19): 120750
Published online Jul 6, 2026. doi: 10.12998/wjcc.120750
Published online Jul 6, 2026. doi: 10.12998/wjcc.120750
Combined homozygous HACE1 and TBCD variants in two siblings with severe early-onset neurodevelopmental disorder: Two case reports
Polina R Korzun, Jeyla O Binnatova, Kristina S Malysheva, Sergey A Laptiev, Anastasiya S Abuzova, Anastasiya O Kipyatkova, Evgeny N Imyanitov, Evgeny N Suspitsin, Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg 194100, Russia
Olga A Kuznetsova, Elena A Yefet, Department of Psychoneurology, St. Petersburg State Pediatric Medical University, St. Petersburg 194100, Russia
Damir A Malekov, Department of Radiology, St. Petersburg State Pediatric Medical University, St. Petersburg 194100, Russia
Evgeny N Imyanitov, Evgeny N Suspitsin, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia
Author contributions: Korzun PR and Malysheva KS designed the research study; Laptiev SA and Abuzova AS analyzed medical histories; Kuznetsova OA, Yefet EA, and Malekov DA monitored and treated the patients; Korzun PR and Binnatova JO performed the genetic testing; Kipyatkova AO contributed to bioinformatics pipelines; Suspitsin EN and Imyanitov EN wrote the manuscript; All authors approved the final version of the article.
AI contribution statement: AI tools (specifically Gemini) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by Russian Science Foundation, No. 24-45-00067.
Informed consent statement: Written informed consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Evgeny N Suspitsin, MD, PhD, Department of Medical Genetics, St. Petersburg State Pediatric Medical University, Litovskaya St., 2, St. Petersburg 194100, Russia. evgeny.suspitsin@gmail.com
Received: March 9, 2026
Revised: May 12, 2026
Accepted: May 27, 2026
Published online: July 6, 2026
Processing time: 117 Days and 2.7 Hours
Revised: May 12, 2026
Accepted: May 27, 2026
Published online: July 6, 2026
Processing time: 117 Days and 2.7 Hours
Core Tip
Core Tip: This report describes two brothers sharing homozygous variants in HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) and tubulin-specific chaperone D (TBCD) genes. Both siblings have severe developmental delay, spastic tetraparesis, early-onset epileptic encephalopathy, and marked cerebral and cerebellar atrophy with corpus callosum hypoplasia, highlighting the challenges of diagnosing overlapping neurogenetic syndromes. Exome testing revealed that they both share the truncating HACE1 c.625C>T variant that explains their clinical symptoms. Conversely, a novel TBCD c.2139T>A allele is likely benign, illustrating the importance of population-specific genetic datasets.