Publication Name	World Journal of Clinical Cases
Manuscript ID	120750
Country	Russia

Category	Genetics & Heredity
Manuscript Type	Case Report
Article Title	Combined homozygous HACE1 and TBCD variants in two siblings with severe early-onset neurodevelopmental disorder: Two case reports
Manuscript Source	Invited Manuscript
All Author List	Polina R Korzun, Jeyla O Binnatova, Kristina S Malysheva, Sergey A Laptiev, Anastasiya S Abuzova, Anastasiya O Kipyatkova, Olga A Kuznetsova, Elena A Yefet, Damir A Malekov, Evgeny N Imyanitov and Evgeny N Suspitsin
Funding Agency and Grant Number	Funding Agency Grant Number Russian Science Foundation 24-45-00067
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
Key Words	HACE1; TBCD; Spastic paraplegia; Psychomotor retardation; Epileptic encephalopathy; Brain atrophy; Corpus callosum hypoplasia; Neurodevelopmental disorder; Pediatrics; Case report
Core Tip	This report describes two brothers sharing homozygous variants in HACE1 and TBCD genes. Both siblings have profound developmental delay, spastic tetraparesis, early-onset epileptic encephalopathy, and marked cerebral and cerebellar atrophy with corpus callosum hypoplasia. The truncating HACE1 c.625C>T variant explains the phenotype compatible with spastic paraplegia and psychomotor retardation with or without seizures, whereas the previously unreported TBCD c.2139T>A allele is unlikely to be causal based on its high prevalence in Chechens and in silico predictions. This report underscores the challenges related to genetic diagnosis of overlapping neurogenetic syndromes, particularly in specific ethnic communities, and exemplifies the value of exome-based testing in early-onset encephalopathy.
Citation	Korzun PR, Binnatova JO, Malysheva KS, Laptiev SA, Abuzova AS, Kipyatkova AO, Kuznetsova OA, Yefet EA, Malekov DA, Imyanitov EN, Suspitsin EN. Combined homozygous HACE1 and TBCD variants in two siblings with severe early-onset neurodevelopmental disorder: Two case reports. World J Clin Cases 2026; In press

Received	2026-03-09 06:19
Peer-Review Started	2026-03-09 06:20
First Decision by Editorial Office Director	2026-04-21 09:47
Return for Revision	2026-04-21 09:47
Revised	2026-05-12 19:40
Publication Fee Transferred
Second Decision by Editor	2026-05-27 02:43
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-27 07:16
Articles in Press	2026-05-27 07:16
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2307-8960 (online)
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