Clinical and molecular characterization of 40 patients with Noonan syndrome
详细信息 查看全文
- 作者：Giovanni Battista Ferrero ; Giuseppina Baldassarre ; Angelo Giovanni Delmonaco ; Elisa Biamino ; Elena Banaudi ; Claudio Carta ; Cesare Rossi ; Margherita Cirillo Silengo
- 关键词：Noonan syndrome ; PTPN11 ; SOS1
- 刊名：European Journal of Medical Genetics
- 出版年：2008
- 出版时间：November-December 2008
- 年：2008
- 卷：51
- 期：6
- 页码：566-572
- 全文大小：238 K
文摘
Noonan syndrome (NS, OMIM 163950) is an autosomal dominant disorder, with a prevalence at birth of 1:1000–1:2500 live births, characterized by short stature, facial and skeletal dysmorphisms, cardiovascular defects and haematological anomalies. Missense mutations of PTPN11 gene account for approximately 50 % of NS cases, while molecular lesions of other genes of the RAS/MAPK pathway – KRAS, SOS1 and RAF1 – play a minor role in the molecular pathogenesis of the disease. Forty patients were enrolled in the study with a PTPN11 mutation detection rate of 31.5 % , including a novel missense mutation, Phe285Ile, in a familial case with high intrafamilial phenotypic variability. All patients negative for PTPN11 mutations were further screened for mutations of the KRAS, SOS1, and RAF1 genes, revealing a Thr266Lys substitution in SOS1 in a single patient, a newborn with a subtle phenotype, characterized by facial dysmorphisms and a mild pulmonic stenosis.