Related Experiment Video

Updated: Feb 28, 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

Next-generation sequencing identifies pathogenic and modifier mutations in a consanguineous Chinese family with

Xinlin Zhang1, Jun Xie, Suhui Zhu

  • 1Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.

Medicine
|June 15, 2017
PubMed

Insights

Genetic modifiers influence hypertrophic cardiomyopathy (HCM) severity. A CACNB2 mutation may worsen MYBPC3-associated HCM, highlighting potential genetic interactions in this complex heart disease.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Epidemiology

Background:

  • Hypertrophic cardiomyopathy (HCM) exhibits significant phenotypic variability, suggesting the influence of genetic modifiers.
  • MYBPC3 mutations are a common cause of familial HCM, yet disease presentation varies widely even within families.

Purpose of the Study:

  • To investigate genetic factors contributing to phenotypic heterogeneity in MYBPC3-associated HCM.
  • To identify potential modifier genes influencing disease severity in a large Chinese family.

Main Methods:

  • Targeted next-generation sequencing was employed to screen for variants in known cardiomyopathy and channelopathy genes.
  • Genotyping was performed to assess the presence of specific mutations in affected and unaffected family members.
  • Exclusion of renin-angiotensin-aldosterone system variants as modifiers.

Main Results:

  • Identified the MYBPC3 c.3624delC mutation in 8 family members with diverse HCM phenotypes.
  • Discovered a novel CACNB2 c.1598C>T (p.Ser533Leu) mutation exclusively in severely affected HCM patients.
  • This CACNB2 mutation was absent in moderately affected individuals, genotype-positive/phenotype-negative individuals, and 550 healthy controls.

Conclusions:

  • The CACNB2 p.Ser533Leu mutation is a potential genetic modifier of MYBPC3-associated familial HCM.
  • Further genetic and functional studies are required to confirm CACNB2's role in HCM pathogenesis.
  • This finding opens new avenues for understanding genetic interactions in hypertrophic cardiomyopathy.

More Related Videos

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia05:51

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

26.5K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.5K

Related Concept Videos

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...
574
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
53
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
9.7K
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
16.0K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
18.8K