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Published on: August 8, 2022
Mutation analysis of the natriuretic peptide precursor B (NPPB) gene in patients with hypertrophic cardiomyopathy
Christine Chiu1, Jodie Ingles, Joanne M Lind
1Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia.
Insights
Genetic analysis of the Natriuretic peptide precursor B (NPPB) gene in hypertrophic cardiomyopathy (HCM) patients revealed no disease-causing mutations. This study indicates NPPB is unlikely to be a significant genetic cause of HCM.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic heart disease often linked to sarcomeric protein mutations.
- A significant portion of HCM cases remain genetically unexplained, prompting investigation into novel genes.
- Natriuretic peptide precursor B (NPPB), a cardiac hormone, is elevated in ventricular hypertrophy, suggesting a potential role in HCM pathogenesis.
Purpose of the Study:
- To investigate the role of the NPPB gene in the genetic etiology of hypertrophic cardiomyopathy.
- To screen for sequence variants in the NPPB gene in a cohort of HCM patients.
Main Methods:
- Genomic DNA from 238 HCM probands was analyzed.
- Coding and intron/exon boundary regions of the NPPB gene were amplified via PCR.
- Sequence variants were identified using high-performance liquid chromatography and direct DNA sequencing.
Main Results:
- Four NPPB sequence variants were found in 9 out of 238 HCM patients.
- These included intronic and synonymous variants, and one non-synonymous variant (Arg47His).
- The Arg47His variant was present in controls, suggesting it is not pathogenic for HCM.
Conclusions:
- No disease-causing mutations in the NPPB gene were identified in this HCM cohort.
- Mutations in NPPB are unlikely to be a common cause of hypertrophic cardiomyopathy.
- Further research is needed to identify the genetic basis of HCM in mutation-negative patients.
Background:
Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous disease caused by mutations in genes that primarily encode sarcomeric proteins. No mutation is identified in up to 40% of HCM patients, suggesting other causative genes exist. Natriuretic peptide precursor B (NPPB; also known as "BNP") is a cardiac hormone involved in body fluid homeostasis and cardiac myocyte growth. NPPB concentrations are markedly increased in patients with ventricular hypertrophy, and it is therefore possible mutations in the NPPB gene could cause HCM.
Methods:
Genomic DNA was extracted from peripheral blood in 238 consecutive probands with HCM. The coding regions and intron/exon boundaries in the NPPB gene were amplified by PCR, and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing.
Results:
Four sequence variants in the NPPB gene were identified in 9 of the 238 probands screened. Two of the variants were intronic, one was a synonymous variant at codon 79, and the final variant resulted in an amino acid substitution from arginine to histidine at codon 47 (Arg47His). The Arg47His variant was identified in a control population consisting of 204 chromosomes at an allelic frequency of 0.5%, and is therefore unlikely to cause disease.
Conclusion:
No disease causing mutations were identified in the NPPB gene in this cohort, indicating that mutations in this gene are unlikely to be responsible for HCM.
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