A low prevalence of MYH7/MYBPC3 mutations among familial hypertrophic cardiomyopathy patients in India

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetic Medicine

Background:

• Familial Hypertrophic Cardiomyopathy (FHC) is a genetically heterogeneous autosomal dominant disorder affecting cardiac muscle.
• Numerous genes, predominantly encoding sarcomere proteins, have been linked to FHC.
• Understanding the genetic basis of FHC in diverse populations is crucial for diagnosis and treatment.

Purpose of the Study:

• To conduct a clinical and molecular analysis of FHC patients from India.
• To identify disease-causing mutations in the MYH7 and MYBPC3 genes.
• To investigate the frequency and spectrum of mutations in the Indian FHC cohort.

Main Methods:

• Echocardiography, clinical assessment, and family history were used for FHC diagnosis.
• Polymerase Chain Reaction-Deoxyribose Nucleic Acid (PCR-DNA) sequencing was employed to analyze MYH7 and MYBPC3 genes.
• Genetic analysis of 55 FHC patient samples from India.

Main Results:

• Mutations in MYH7 and MYBPC3 were identified in 19 out of 55 FHC patients.
• MYBPC3 mutations were found in 12 patients, and MYH7 mutations in five; two patients had double heterozygosity.
• Four novel MYBPC3 mutations and one novel MYH7 mutation were discovered; missense mutations often affected conserved residues.

Conclusions:

• MYBPC3 mutations are more frequent than MYH7 mutations in the studied Indian FHC population.
• The identified novel mutations contribute to the genetic landscape of FHC.
• Molecular analysis is essential for diagnosing FHC and understanding its genetic heterogeneity.