Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy.

Details

Serval ID
serval:BIB_6BB4100832F1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy.
Journal
Medicina
Author(s)
Abdallah A.M., Carlus S.J., Al-Mazroea A.H., Alluqmani M., Almohammadi Y., Bhuiyan Z.A., Al-Harbi K.M.
ISSN
1648-9144 (Electronic)
ISSN-L
1010-660X
Publication state
Published
Issued date
15/01/2019
Peer-reviewed
Oui
Volume
55
Number
1
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.
Keywords
Cardiac Myosins/genetics, Cardiomyopathy, Dilated/genetics, Cohort Studies, Echocardiography, Female, Genetic Variation, High-Throughput Nucleotide Sequencing, Humans, Infant, Infant Health, Laminin/genetics, Male, Mutation, Missense, Myosin Heavy Chains/genetics, Pedigree, Rare Diseases/genetics, Saudi Arabia, LAMA4, MYH7, digenic, dilated cardiomyopathy, targeted gene sequencing
Pubmed
Web of science
Open Access
Yes
Create date
20/02/2019 13:16
Last modification date
20/08/2019 14:25
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