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Mutation screening of the PTPN11 gene in hypertrophic cardiomyopathy
Giuseppe Limongelli1, Lorraine Hawkes, Raffaele Calabro
1Department of Medicine, University College London and University College London Hospitals Trust, Cobbold Laboratories, 7th Floor, Jules Thorn Institute, Middlesex Hospital, 48 Riding House Street, London W1W 7EY, UK.
Insights
Mutations in the PTPN11 gene are not a cause of hypertrophic cardiomyopathy (HCM) when Noonan or LEOPARD syndromes are absent. This study screened 250 HCM patients for PTPN11 mutations, finding none.
Area of Science:
- Genetics
- Cardiology
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease and a leading cause of sudden cardiac death.
- HCM is typically caused by mutations in sarcomeric protein genes, but mutations are found in only 50-60% of patients, suggesting other genetic factors.
- Noonan and LEOPARD syndromes, caused by PTPN11 mutations, feature cardiac defects including HCM, raising questions about PTPN11's role in isolated HCM.
Purpose of the Study:
- To investigate the potential involvement of the PTPN11 gene in the pathogenesis of hypertrophic cardiomyopathy (HCM).
- To screen for PTPN11 mutations in a cohort of HCM patients, particularly those without known sarcomeric mutations.
Main Methods:
- Mutation screening of the entire coding region of the PTPN11 gene.
- Analysis of 250 hypertrophic cardiomyopathy (HCM) probands, including 200 without sarcomeric gene mutations and 50 with known sarcomeric mutations.
Main Results:
- No mutations in the PTPN11 gene were identified in any of the 250 HCM probands studied.
- The absence of PTPN11 mutations suggests it is not a significant cause of HCM in the absence of syndromic features.
Conclusions:
- Mutations in the PTPN11 gene are unlikely to be a cause of hypertrophic cardiomyopathy (HCM) when Noonan or LEOPARD syndromes are not present.
- Further research into other genetic factors is warranted to explain the remaining cases of HCM.
- The study provides evidence against PTPN11 as a common cause of isolated HCM.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease and a major cause of sudden death. It is an autosomal dominant disorder predominantly caused by mutations in genes encoding for sarcomeric proteins. Only 50-60% of HCM probands have mutations in known genes suggesting the presence of additional disease genes. Noonan and LEOPARD syndromes are characterised by multiple dysmorphia and cardiac defects with HCM present in approximately 20% of cases. Both syndromes are caused by mutations in the PTPN11 gene which codes for the protein tyrosine phosphatase SHP-2. It is suspected but unproven that the cardiac phenotype may predominate or even be present in isolation. In order to determine possible involvement of this gene in the pathogenesis of HCM, we performed mutation screening of the PTPN11 coding region in 250 selected HCM probands (200 patients without mutations in sarcomeric genes and 50 with identified mutations). No mutations in PTPN11 were identified. Our data suggests that mutations in the PTPN11 gene are not a cause of HCM in the absence of Noonan/LEOPARD syndromes.
