Next Article in Journal
Pulmonary Endarterectomy in Latvia: A National Experience
Previous Article in Journal
Associations between Red Blood Cell Transfusions and Necrotizing Enterocolitis in Very Low Birth Weight Infants: Ten-Year Data of a Tertiary Neonatal Unit
Open AccessArticle

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

1
West Midlands Regional Genetics Laboratory, The Birmingham Women’s and Children’s NHS Foundation Trus, Birmingham B15 2TT, UK
2
Cardiogenetics Unit, Pediatrics Department, College of Medicine, Taibah University, Al-Madinah 30001, Saudi Arabia
3
Security Forces Medical Centre, Al-Madinah 30010, Saudi Arabia
4
Unit of Cardiogenetics Research, Division of Genetic Medicine, BT.02. 251, Beaumont 29, 1011 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Medicina 2019, 55(1), 17; https://doi.org/10.3390/medicina55010017
Received: 23 November 2018 / Revised: 9 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
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. View Full-Text
Keywords: targeted gene sequencing; dilated cardiomyopathy; digenic; MYH7; LAMA4; Saudi Arabia targeted gene sequencing; dilated cardiomyopathy; digenic; MYH7; LAMA4; Saudi Arabia
Show Figures

Figure 1

MDPI and ACS Style

Abdallah, A.M.; Carlus, S.J.; Al-Mazroea, A.H.; Alluqmani, M.; Almohammadi, Y.; Bhuiyan, Z.A.; Al-Harbi, K.M. Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy. Medicina 2019, 55, 17.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop