Brasil Amanda Salem, Malaquias Alexsandra C, Wanderley Luciana Turolla, Kim Chong Ae, Krieger José Eduardo, Jorge Alexander A L, Pereira Alexandre C, Bertola Débora Romeo
Genetics Unit, Children’s Institute, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2010 Nov;54(8):717-22. doi: 10.1590/s0004-27302010000800009.
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.
努南综合征（NS）是一种常染色体显性疾病，具有可变的表型表达，其特征为身材矮小、面部畸形和心脏病。RAS/MAPK信号通路的不同基因与该综合征有关，最常见的是：PTPN11、SOS1、RAF1和KRAS。本研究的目的是报告一名患有努南综合征的患者，其RAS/MAPK通路的两个基因存在突变，以确定这些突变是否会导致更严重的表型表达。我们对PTPN11、SOS1、RAF1和KRAS基因进行了直接测序。我们发现了两个杂合的已报道突变：分别在PTPN11和SOS1基因中的p.N308D和p.R552G。该患者具有与仅一个基因突变的努南综合征患者相似的典型临床特征，甚至与该患者中鉴定出的相同突变的患者也相似。未观察到更严重或非典型的表型，这表明这些突变没有表现出累加效应。
