PTPN11 and KRAS Gene Analysis in Patients with Noonan and Noonan-Like Syndromes

Autor(es)

Brasil, Amanda Salem ; Pereira, Alexandre C. ^[1] ; Wanderley, Luciana Turolla ; Kim, Chong Ae ; Malaquias, Alexsandra C. ^[2] ; Jorge, Alexander A. L. ^[2] ; Krieger, Jose Eduardo ^[1] ; Bertola, Debora Romeo ^[3]

Afiliação do(s) autor(es)

^[1] InCor, Lab Genet & Cardiol Mol, Sao Paulo - Brazil

^[2] Unidade Endocrinol Desenvolvimento, Lab Hormominos & Genet Mol, Sao Paulo - Brazil

^[3] Hosp Clin Sao Paulo, Fac Med Sao Paulo, Unidade Genet, Inst Crianca, BR-05403900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GENETIC TESTING AND MOLECULAR BIOMARKERS; v. 14, n. 3, p. 425-432, JUN 2010.
• Citações Web of Science: 19

Resumo

Noonan and Noonan-like syndromes are disorders of dysregulation of the rat sarcoma viral oncogene homolog (RAS)-mitogen-activated protein kinase signaling pathway. In Noonan syndrome (NS), four genes of this pathway (PTPN11, SOS1, RAF1, and KRAS) are responsible for roughly 70% of the cases. We analyzed PTPN11 and KRAS genes by bidirectional sequencing in 95 probands with NS and 29 with Noonan-like syndromes, including previously reported patients already screened for PTPN11 gene mutations. In the new patients with NS, 20/46 (43%) showed a PTPN11 gene mutation, two of them novel. In our total cohort, patients with NS and a PTPN11 mutation presented significantly higher prevalence of short stature (p = 0.03) and pulmonary valve stenosis (p = 0.01), and lower prevalence of hypertrophic cardiomyopathy (p = 0.01). Only a single gene alteration, of uncertain role, was found in the KRAS gene in an NS patient also presenting a PTPN11 gene mutation. We further analyzed the influence in clinical variability of three frequent polymorphisms found in the KRAS gene and no statistically significant difference was observed among the frequency of clinical findings regarding the studied polymorphisms. (AU)

• Processo FAPESP: 08/50184-2 - Determinantes geneticos na sindrome de noonan e sindromes noonan-like: investigacao clinica e molecular.
• Beneficiário: Débora Romeo Bertola
• Modalidade de apoio: Auxílio à Pesquisa - Regular