Homozygous Truncating Mutation in NRAP Gene Identified by Whole Exome Sequencing in a Patient with Dilated Cardiomyopathy

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jun 15

PMID 28611399

Citations 20

Authors

Grazyna T Truszkowska

Zofia T Bilinska

Angelika Muchowicz

Agnieszka Pollak

Anna Biernacka

Katarzyna Kozar-Kaminska

Piotr Stawinski

Piotr Gasperowicz

Joanna Kosinska

Tomasz Zielinski

Rafal Ploski

Affiliations

Soon will be listed here.

Abstract

The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband's brother. The expression of the NRAP protein was undetectable in the patient's heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.

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