Related Experiment Video

Updated: Feb 14, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

4.3K

Novel α-Actin Gene Mutation p.(Ala21Val) Causing Familial Hypertrophic Cardiomyopathy, Myocardial Noncompaction, and

Andrea Frustaci1,2, Alessandro De Luca3, Valentina Guida3

  • 1Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and GeriatricSciences, Sapienza University, Rome, Italy biocard@inmi.it.

Journal of the American Heart Association
|February 15, 2018
PubMed

Insights

A new mutation in the ACTC1 gene, p.(Ala21Val), causes familial hypertrophic cardiomyopathy and left ventricular (LV) myocardial noncompaction. This genetic defect leads to myofibrillar and intercalated disc alterations in heart muscle cells.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Cardiology

Background:

  • Mutations in the alpha-actin gene (ACTC1) are linked to various cardiac conditions, including hypertrophic cardiomyopathy (HCM) and left ventricular (LV) myocardial noncompaction.
  • A novel ACTC1 mutation has been identified that cosegregates with familial HCM and LV myocardial noncompaction characterized by transmural crypts.

Purpose of the Study:

  • To investigate a novel ACTC1 mutation in an Italian family presenting with familial hypertrophic cardiomyopathy and left ventricular myocardial noncompaction.
  • To elucidate the molecular and cellular mechanisms underlying the observed cardiac phenotypes.

Main Methods:

  • Genetic analysis using next-generation sequencing was performed on affected family members.
  • Cardiac imaging techniques including 2D echocardiography and cardiac magnetic resonance were utilized.
  • Invasive cardiac studies, histology, and electron microscopy were conducted on affected individuals.

Main Results:

  • A novel, unreported p.(Ala21Val) mutation in the ACTC1 gene was identified in all affected family members.
  • All affected individuals exhibited left ventricular (LV) myocardial noncompaction, with some showing progressive LV hypertrophy.
  • Histological and electron microscopy revealed myocardiocyte detachment, myofibrillar disarray, and degraded intercalated discs.

Conclusions:

  • The novel p.(Ala21Val) mutation in ACTC1 is causative of familial hypertrophic cardiomyopathy and LV myocardial noncompaction.
  • The mutation leads to significant alterations in myofibrils and intercalated discs, resulting in cardiac dysfunction.
Abstract

Keywords:
familial hypertrophic cardiomyopathygene mutationmyocardial noncompaction

More Related Videos

Aip1p Dynamics Are Altered by the R256H Mutation in Actin08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.4K
Quantification of Colonic Stem Cell Mutations07:53

Quantification of Colonic Stem Cell Mutations

Published on: September 25, 2015

7.0K

Related Concept Videos

Gene Families01:57

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
10.0K
Gene Families01:57

Gene Families

3.9K
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
532
Protein Families02:47

Protein Families

Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism.   Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members.   If these new proteins contain similar amino acids in key...
17.2K
Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
64.7K
Mutations01:39

Mutations

Overview
94.7K