CAP2 mutation leads to impaired actin dynamics and associates with supraventricular tachycardia and dilated cardiomyopathy.
Actins
/ metabolism
Adaptor Proteins, Signal Transducing
/ chemistry
Alleles
Amino Acid Sequence
Cardiomyopathy, Dilated
/ diagnosis
Child
Child, Preschool
Consanguinity
DNA Mutational Analysis
Female
Fibroblasts
Genetic Association Studies
Genetic Predisposition to Disease
Homozygote
Humans
Male
Membrane Proteins
/ chemistry
Models, Molecular
Mutation
Pedigree
RNA Splicing
Structure-Activity Relationship
Tachycardia, Supraventricular
/ diagnosis
Cap2
actin polymerization
arrhythmias
dilated cardiomyopathy
splice mutation
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
24
05
2018
revised:
10
10
2018
accepted:
22
10
2018
pubmed:
7
12
2018
medline:
23
5
2020
entrez:
7
12
2018
Statut:
ppublish
Résumé
Dilated cardiomyopathy (DCM) is a primary myocardial disease leading to contractile dysfunction, progressive heart failure and excessive risk of sudden cardiac death. Around half of DCM cases are idiopathic, and genetic factors seem to play an important role. We investigated a possible genetic cause of DCM in two consanguineous children from a Bedouin family. Using exome sequencing and searching for rare homozygous variations, we identified a nucleotide change in the donor splice consensus sequence of exon 7 in This is the first report of a recessive deleterious mutation in CAP2 and its association with DCM in humans. The clinical phenotype recapitulates the damaging effects on the heart observed in
Sections du résumé
BACKGROUND
Dilated cardiomyopathy (DCM) is a primary myocardial disease leading to contractile dysfunction, progressive heart failure and excessive risk of sudden cardiac death. Around half of DCM cases are idiopathic, and genetic factors seem to play an important role.
AIM
We investigated a possible genetic cause of DCM in two consanguineous children from a Bedouin family.
METHODS AND RESULTS
Using exome sequencing and searching for rare homozygous variations, we identified a nucleotide change in the donor splice consensus sequence of exon 7 in
CONCLUSIONS
This is the first report of a recessive deleterious mutation in CAP2 and its association with DCM in humans. The clinical phenotype recapitulates the damaging effects on the heart observed in
Identifiants
pubmed: 30518548
pii: jmedgenet-2018-105498
doi: 10.1136/jmedgenet-2018-105498
doi:
Substances chimiques
Actins
0
Adaptor Proteins, Signal Transducing
0
CAP2 protein, human
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
228-235Informations de copyright
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.