A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy

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Tarih

2024-12-10

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

S. Karger AG

Erişim Hakkı

info:eu-repo/semantics/closedAccess

Özet

Background: HERC2 encodes an E3 ubiquitin ligase that plays a critical role in brain development. Loss-of-function variants are associated with severe neurodevelopmental phenotypes, including intellectual disability, epilepsy, and various structural anomalies. This report aimed to expand phenotypic spectrum of HERC2-related disorders, including an unusual cardiac manifestation. Case Presentation: The proband, a male infant born to consanguineous parents, presented with myoclonia-like eyelid movements at 50-days old and subsequently developed severe neuromotor regression and choreoathetotic movements. Brain magnetic resonance imaging revealed diffuse cerebral atrophy, corpus callosum thinning, and bilateral pachygyria. He also exhibited distinct dysmorphic features and dilated cardiomyopathy, confirmed by echocardiography. His sibling presented with similar features, including severe developmental delay and dilated cardiomyopathy. Whole-exome sequencing identified a homozygous likely pathogenic c.7645C>T (p.Gln2549Ter) variant in the HERC2 gene. This case report is significant as it describes dilated cardiomyopathy in MRT38, a manifestation not previously associated with HERC2 variants. The unusual cardiac phenotype suggests a potential link between HERC2 dysfunction and mitochondrial impairment, contributing to cardiomyopathy. Conclusion: These patients underscore the importance of recognizing novel clinical features associated with the HERC2 LoF variants, which can guide disease characterization and patient management.

Açıklama

Anahtar Kelimeler

Developmental delay, Dysmorphology, HERC2, Mitochondrial impairment, Neuronal migration disorders, Whole-exome sequencing

Kaynak

Molecular Syndromology

WoS Q Değeri

Scopus Q Değeri

N/A

Cilt

Sayı

Künye

Şenol, H. B., Günay, Ç., Polat, A. İ., Aydın, A., Hiz, A. S., & Yiş, U. (2024). A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy. Molecular Syndromology, 1-11.