Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines
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چکیده
منابع مشابه
Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.
Noonan syndrome (NS; MIM 163950) is an autosomal dominant disorder and a member of a family of developmental disorders termed "RASopathies," which are caused mainly by gain-of-function mutations in genes encoding RAS/MAPK signaling pathway proteins. Whole exome sequencing (WES) and trio-based genomic triangulation of a 15-year-old female with a clinical diagnosis of NS and concomitant cardiac h...
متن کاملElevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines.
Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients car...
متن کاملIn vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy
Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in m...
متن کاملClinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome.
M ultiple lentigines LEOPARD syndrome (MIM 151100) is an autosomal dominant multiple congenital anomaly syndrome, with high penetrance and markedly variable expression. The acronym LEOPARD was coined by Gorlin et al. in 1971 as a mnemonic of the major features of this disorder: multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retard...
متن کاملONLINE MUTATION REPORT Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome
M ultiple lentigines LEOPARD syndrome (MIM 151100) is an autosomal dominant multiple congenital anomaly syndrome, with high penetrance and markedly variable expression. The acronym LEOPARD was coined by Gorlin et al. in 1971 as a mnemonic of the major features of this disorder: multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retard...
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ژورنال
عنوان ژورنال: Journal of Clinical Investigation
سال: 2016
ISSN: 0021-9738,1558-8238
DOI: 10.1172/jci80396