Whole-exome sequencing identifies a novel mutation of GPD1L (R189X) associated with familial conduction disease and sudden death.

Journal of Cellular and Molecular Medicine
Hao HuangRong Xiang

Abstract

Cardiac conduction disease (CCD) is a serious disorder and the leading cause of mortality worldwide. It is characterized by arrhythmia, syncope or even sudden cardiac death caused by the dysfunction of cardiac voltage-gated channel. Previous study has demonstrated that mutations in genes encoding voltage-gated channel and related proteins were the crucial genetic lesion of CCD. In this study, we employed whole-exome sequencing to explore the potential causative genes in a Chinese family with ventricular tachycardia and syncope. A novel nonsense mutation (c.565C>T/p.R189X) of glycerol-3-phosphate dehydrogenase-like (GPD1L) was identified and co-segregated with the affected family members. GPD1L is a crucial interacting protein of SCN5A, a gene encoded sodium channel α-subunit Nav 1.5 and mainly associated with Brugada syndrome (BrS). The novel mutation (c.565C>T/p.R189X) may result in a premature stop codon at position 189 in exon 4 of the GPD1L gene and lead to functional haploinsufficiency of GPD1L due to mRNA carrying this mutation will be degraded by nonsense-mediated mRNA decay, which has been confirmed by Western blot in HEK293 cells transfected HIS-GPD1L plasmid. The levels of GPD1L decreasing may disturb the function of ...Continue Reading

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Citations

Mar 3, 2018·International Journal of Molecular Sciences·Anna Garcia-Elias, Begoña Benito
Apr 9, 2021·Frontiers in Medicine·Dragan PrimoracJohannes Brachmann
Sep 25, 2021·The Journal of Gene Medicine·Hao HuangRong Xiang

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

SIFT
MutationTaster
pEnter
PolyPhen

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