Department of Human Genetics, University of Leuven, Leuven, Belgium.
Genes Chromosomes Cancer. 2010 Mar;49(3):242-52. doi: 10.1002/gcc.20735.
Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1. We performed SOS1, RAF1, BRAF, MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11- and KRAS-negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1-positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations.
努南综合征（NS）是一种常染色体显性遗传病，由 PTPN11、KRAS、SOS1 和 RAF1 基因突变引起。我们对 102 例 PTPN11 和 KRAS 阴性 NS 患者进行了 SOS1、RAF1、BRAF、MEK1 和 MEK2 突变分析，发现 10 例存在 SOS1 致病性突变，4 例存在 RAF1 突变，2 例存在 BRAF 突变。发现了 3 种新的 SOS1 突变。其中一种被归类为罕见良性变异，另一种仍未分类。我们证实 SOS1 阳性患者中肺动脉瓣狭窄和外胚层异常的患病率很高。3 例 SOS1 突变患者患有肿瘤（胚胎横纹肌肉瘤、睾丸支持细胞瘤和皮肤颗粒细胞瘤）。1 例 RAF1 突变患者的病变提示为巨细胞瘤。这是首例描述携带 SOS1 种系突变的 NS 患者存在不同肿瘤类型的报告。
