Mutation screening of the PTPN11 gene in hypertrophic cardiomyopathy.
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.
Limongelli
Giuseppe
G
Department 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.
Hawkes
Lorraine
L
Calabro
Raffaele
R
McKenna
William J
WJ
Syrris
Petros
P
D000328:Adult; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000201:enzymology* / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases