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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Brasil, Amanda Salem [1] ; Malaquias, Alexsandra C. [2] ; Wanderley, Luciana Turolla [1] ; Kim, Chong Ae [1] ; Krieger, Jose Eduardo [3] ; Jorge, Alexander A. L. [4] ; Pereira, Alexandre C. [3] ; Bertola, Debora Romeo [1]
Total Authors: 8
[1] Univ Sao Paulo, Fac Med, Genet Unit, Childrens Inst, Hosp Clin, Sao Paulo - Brazil
[2] HC FMUSP, Endocrinol Dev Unit, Hormone & Mol Genet Lab, BR-05403900 Sao Paulo - Brazil
[3] HC FMUSP, Lab Genet & Mol Cardiol, Hearts Inst InCor, BR-05403900 Sao Paulo - Brazil
[4] HC FMUSP, Endocrinol Genet Unit LIM 25, Discipline Endocrinol, BR-05403900 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Arquivos Brasileiros de Endocrinologia e Metabologia; v. 54, n. 8, SI, p. 717-722, NOV 2010.
Web of Science Citations: 10

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)