Ko Jung Min, Kim Jae-Min, Kim Gu-Hwan, Yoo Han-Wook
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Genome Research Center for Birth defects and Genetic Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
J Hum Genet. 2008;53(11-12):999-1006. doi: 10.1007/s10038-008-0343-6. Epub 2008 Nov 20.
After 2006, germline mutations in the KRAS, SOS1, and RAF1 genes were reported to cause Noonan syndrome (NS), in addition to the PTPN11 gene, and now we can find the etiology of disease in approximately 60-70% of NS cases. The aim of this study was to assess the correlation between phenotype and genotype by molecular analysis of the PTPN11, SOS1, KRAS, and RAF1 genes in 59 Korean patients with NS. We found disease-causing mutations in 30 (50.8%) patients, which were located in the PTPN11 (27.1%), SOS1 (16.9%), KRAS (1.7%), and RAF1 (5.1%) genes. Three novel mutations (T59A in PTPN11, K170E in SOS1, S259T in RAF1) were identified. The patients with PTPN11 mutations showed higher prevalences of patent ductus arteriosus and thrombocytopenia. The patients with SOS1 mutations had a lower prevalence of delayed psychomotor development. All patients with RAF1 mutations had hypertrophic cardiomyopathy. Typical facial features and auxological parameters were, on statistical analysis, not significantly different between the groups. The molecular defects of NS are genetically heterogeneous and involve several genes other than PTPN11 related to the RAS-MAPK pathway.
2006年后，除PTPN11基因外，据报道KRAS、SOS1和RAF1基因的种系突变也可导致努南综合征（NS），现在我们可以在大约60%-70%的NS病例中找到病因。本研究的目的是通过对59例韩国NS患者的PTPN11、SOS1、KRAS和RAF1基因进行分子分析，评估表型与基因型之间的相关性。我们在30例（50.8%）患者中发现了致病突变，这些突变分别位于PTPN11基因（27.1%）、SOS1基因（16.9%）、KRAS基因（1.7%）和RAF1基因（5.1%）。鉴定出三个新突变（PTPN11基因中的T59A、SOS1基因中的K170E、RAF1基因中的S259T）。PTPN11基因突变的患者动脉导管未闭和血小板减少症的患病率较高。SOS1基因突变的患者精神运动发育迟缓的患病率较低。所有RAF1基因突变的患者均患有肥厚型心肌病。经统计学分析，各组之间典型的面部特征和体格测量参数无显著差异。NS的分子缺陷在遗传上具有异质性，涉及除与RAS-MAPK途径相关的PTPN11基因以外与RAS-MAPK途径相关的几个基因以外的其他几个基因。
