Missense variants in the spectrin repeat domain of DSP are associated with arrhythmogenic cardiomyopathy: A family report and systematic review.
cardiomyopathy
desmoplakin
missense variant
spectrin repeat domain
sudden cardiac death
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
05
2020
revised:
16
06
2020
accepted:
11
07
2020
pubmed:
19
8
2020
medline:
2
6
2021
entrez:
19
8
2020
Statut:
ppublish
Résumé
Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
Identifiants
pubmed: 32808748
doi: 10.1002/ajmg.a.61799
doi:
Substances chimiques
DSP protein, human
0
Desmoplakins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2359-2368Subventions
Organisme : CIHR
ID : 428321
Pays : Canada
Informations de copyright
© 2020 Wiley Periodicals LLC.
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