Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy

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 invo...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-06, Vol.7 (1), p.3362-5, Article 3362
Main Authors: Truszkowska, Grażyna T., Bilińska, Zofia T., Muchowicz, Angelika, Pollak, Agnieszka, Biernacka, Anna, Kozar-Kamińska, Katarzyna, Stawiński, Piotr, Gasperowicz, Piotr, Kosińska, Joanna, Zieliński, Tomasz, Płoski, Rafał
Format: Article
Language:English
Subjects:
38/77
45/23
631/208/514/2254
692/4019/592/2727
82/80
Actin
Adult
Cardiac muscle
Cardiomyopathy
Cardiomyopathy, Dilated - genetics
Cardiomyopathy, Dilated - pathology
Cytoskeleton
Dilated cardiomyopathy
Female
Genotype
Genotyping
Heart diseases
Homozygote
Humanities and Social Sciences
Humans
Isoforms
Male
multidisciplinary
Muscle Proteins - genetics
Muscles
Mutation
Nonsense mutation
Pedigree
Proteins
Risk factors
Science
Science (multidisciplinary)
Stop codon
Whole Exome Sequencing - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-03189-8