A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy.
Details
Serval ID
serval:BIB_73E78E497318
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy.
Journal
Genes
ISSN
2073-4425 (Electronic)
ISSN-L
2073-4425
Publication state
Published
Issued date
13/03/2023
Peer-reviewed
Oui
Volume
14
Number
3
Pages
707
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
GEMIN5 is a multifunctional RNA-binding protein required for the assembly of survival motor neurons. Several bi-allelic truncating and missense variants in this gene are reported to cause a neurodevelopmental disorder characterized by cerebellar atrophy, intellectual disability (ID), and motor dysfunction. Whole exome sequencing of a Pakistani consanguineous family with three brothers affected by ID, cerebral atrophy, mobility, and speech impairment revealed a novel homozygous 3bp-deletion NM_015465.5:c.3162_3164del that leads to the loss of NM_015465.5 (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) amino acid in one of the α-helixes of the tetratricopeptide repeats of GEMIN5. In silico 3D representations of the GEMIN5 dimerization domain show that this variant likely affects the orientation of the downstream sidechains out of the helix axis, which would affect the packing with neighboring helices. The phenotype of all affected siblings overlaps well with previously reported patients, suggesting that NM_015465.5: c.3162_3164del (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) is a novel GEMIN5 pathogenic variant. Overall, our data expands the molecular and clinical phenotype of the recently described neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) syndrome.
Keywords
Male, Humans, Intellectual Disability/etiology, Tetratricopeptide Repeat, Pedigree, Neurodevelopmental Disorders/complications, Atrophy/genetics, SMN Complex Proteins/genetics, TPR domain, aspartic acid deletion, autosomal recessive, cerebral atrophy, consanguinity, intellectual disability, neurodevelopmental disorder
Pubmed
Web of science
Open Access
Yes
Create date
06/04/2023 13:18
Last modification date
21/04/2023 7:11