Musante Luciana, Kehl Hans G, Majewski Frank, Meinecke Peter, Schweiger Susann, Gillessen-Kaesbach Gabriele, Wieczorek Dagmar, Hinkel Georg K, Tinschert Sigrid, Hoeltzenbein Maria, Ropers Hans-Hilger, Kalscheuer Vera M
Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
Eur J Hum Genet. 2003 Feb;11(2):201-6. doi: 10.1038/sj.ejhg.5200935.
Noonan syndrome (NS) is a relatively common, but genetically heterogeneous autosomal dominant malformation syndrome. Characteristic features are proportionate short stature, dysmorphic face, and congenital heart defects. Only recently, a gene involved in NS could be identified. It encodes the non-receptor protein tyrosine phosphatase SHP-2, which is an important molecule in several intracellular signal transduction pathways that control diverse developmental processes, most importantly cardiac semilunar valvulogenesis. We have screened this gene for mutations in 96 familial and sporadic, well-characterised NS patients and identified 15 different missense mutations in a total of 32 patients (33%), including 23 index patients. Most changes clustered in one exon which encodes parts of the N-SH2 domain. Five of the mutations were recurrent. Interestingly, no mutations in the PTPN11 gene were detected in five additional patients with cardio-facio-cutaneous (CFC) syndrome, which shows clinical similarities to NS.
努南综合征（NS）是一种相对常见但基因异质性的常染色体显性畸形综合征。其特征性表现为匀称性身材矮小、面部畸形和先天性心脏缺陷。直到最近，才鉴定出一种与努南综合征相关的基因。它编码非受体蛋白酪氨酸磷酸酶SHP-2，这是几种细胞内信号转导途径中的重要分子，这些途径控制着多种发育过程，最重要的是心脏半月瓣的形成。我们对96例家族性和散发性、特征明确的努南综合征患者的该基因进行了突变筛查，在总共32例患者（33%）中鉴定出15种不同的错义突变，其中包括23例先证者。大多数变化集中在一个编码N-SH2结构域部分的外显子中。其中5种突变是反复出现的。有趣的是，在另外5例患有心脏-颜面-皮肤综合征（CFC）的患者中未检测到PTPN11基因的突变，该综合征与努南综合征有临床相似性。
