Atik Tahir, Aykut Ayca, Hazan Filiz, Onay Huseyin, Goksen Damla, Darcan Sukran, Tukun Ajlan, Ozkinay Ferda
Division of Genetics, Department of Pediatrics, School of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.
Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey.
Indian J Pediatr. 2016 Jun;83(6):517-21. doi: 10.1007/s12098-015-1998-6. Epub 2016 Jan 28.
To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations.
In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed.
Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes.
By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.
评估努南综合征患者中PTPN11基因突变谱，并研究基因型与表型的相关性。
本研究纳入了20例携带PTPN11基因突变的努南综合征患者。对患者进行了详细的临床和体格评估。为确定遗传病例，对所有突变阳性患者的父母进行了分析。
研究组检测到13种不同的PTPN11突变，其中2种为新突变。这些突变包括11种错义突变：p.G60A、p.D61N、p.Y62D、p.Y63C、p.E69Q、p.Q79R、p.Y279C、p.N308D、p.N308S、p.M504V、p.Q510R，以及2种新的错义突变：p.I56V和p.I282M。发现心脏异常和身材矮小的发生率分别为80%和80%。外显子8突变的患者未观察到智力发育迟缓。未检测到其他表型特征与基因型之间存在显著相关性。
通过确定基因型与表型的相关性，本研究提供了不同PTPN11突变的努南综合征患者所观察到的表型信息。
