Cardiac α-Actin ( ACTC1 ) Gene Mutation Causes Atrial-Septal Defects Associated With Late-Onset Dilated Cardiomyopathy
Key result
A heterozygous ACTC1 mutation (p. Gly247Asp) caused a combined phenotype of atrial septal defect and late-onset dilated cardiomyopathy, present in 15 affected and absent in 63 healthy family members.
Why the study?
Familial atrial septal defect has been attributed primarily to mutations in cardiac transcription factors, prompting characterization of a novel ACTC1 mutation in a family with ASD and late-onset dilated cardiomyopathy.
Does a mutation in the ACTC1 gene cause familial atrial septal defect associated with late-onset dilated cardiomyopathy?
Population
78 members of a large, multi-generational family
Comparison
15 affected members with ACTC1 mutation vs 63 healthy family members
Design
Genome-wide linkage analysis and mechanistic molecular study
Authors
Discussion
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Member takes
Implication
May support ACTC1 testing and HF surveillance in familial ASD-DCM; extends phenotypes but leaves validation open.
Study Design
Type
Observational (n=78)
Structured PICO
Does a mutation in the ACTC1 gene cause familial atrial septal defect associated with late-onset dilated cardiomyopathy?
P
Population
78 members of a multi-generational family evaluated for familial atrial septal defect and late-onset dilated cardiomyopathy.
E
Exposure
Presence of a heterozygous, nonsynonymous ACTC1 (cardiac α-actin) mutation (p.Gly247Asp) / overexpression of mutant ACTC1.
C
Comparator
Healthy family members without the mutation / native human ACTC1.
O
Outcome
Identification of the genetic locus and specific mutation causing the combined phenotype, and characterization of its molecular and cellular consequences.surrogate
A novel ACTC1 mutation (p.Gly247Asp) causes a combined phenotype of familial atrial septal defect and late-onset dilated cardiomyopathy through defective actin polymerization, suggesting patients with ASD and this mutation should be monitored for heart failure.
Cite This Study
Frank et al. (2019) conducted an observational in Atrial septal defect and late-onset dilated cardiomyopathy (n=78). ACTC1 (p. Gly247Asp) mutation vs. Absence of ACTC1 mutation was evaluated on Atrial septal defect and late-onset dilated cardiomyopathy. A heterozygous ACTC1 mutation (p. Gly247Asp) caused a combined phenotype of atrial septal defect and late-onset dilated cardiomyopathy, present in 15 affected and absent in 63 healthy family members.