Co-occurring PTPN11 and SOS1 gene mutations in Noonan syndrome: does this predict a more severe phenotype?

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Arquivos Brasileiros de Endocrinologia e Metabologia; v. 54, n. 8, p. 6-pg., 2010-11-01.

Resumo

Noonan syndrome (NS) is an autosomal dominant disorder, with variable phenotypic expression, characterized by short stature, facial dysmorphisms and heart disease. Different genes of the RAS/MAPK signaling pathway are responsible for the syndrome, the most common are: PTPN11, SOS1, RAF1, and KRAS. The objective of this study was to report a patient with Noonan syndrome presenting mutations in two genes of RAS/MAPK pathway in order to establish whether these mutations lead to a more severe expression of the phenotype. We used direct sequencing of the PTPN11, SOS1, RAF1, and KRAS genes. We have identified two described mutations in heterozygosity: p.N308D and p.R552G in the genes PTPN11 and SOS1, respectively. The patient has typical clinical features similar to the ones with NS and mutation in only one gene, even those with the same mutation identified in this patient. A more severe or atypical phenotype was not observed, suggesting that these mutations do not exhibit an additive effect. Arq Bras Endocrinol Metab. 2010,54(8):717-22 (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
• Processo FAPESP: 07/59555-0 - Estudo da relação genótipo: fenótipo na síndrome de Noonan em pacientes com mutações identificadas nos genes PTPN11, RAF1, SOS1 e KRAS
• Beneficiário: Alexsandra Christianne Malaquias de Moura Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado