BACKGROUND Noonan syndrome (NS), an autosomal dominant developmental genetic disorder, is caused by germline mutations in genes associated with the RAS / mitogen-activated protein kinase (MAPK) pathway. In several studies PTPN11 is one of the genes with a significant number of pathogenic variants in NS-affected patients. Therefore, clinically diagnosed NS individuals are initially tested for pathogenic variants in PTPN11 gene to confirm the relationship before studying genotype-phenotype correlation. METHODS Individuals (363) with clinically diagnosed NS from four hospitals in South India were recruited and the exons of PTPN11 gene were sequenced. RESULTS Thirty-two previously described pathogenic variants in eight different exons in PTPN11 gene were detected in 107 patients, of whom 10 were familial cases. Exons 3, 8 and 13 had the highest number of pathogenic variants. The most commonly identified pathogenic variants in this series were in exon 8 (c.922A > G, c.923A > G), observed in 22 of the affected. Congenital cardiac anomalies were present in 84% of the mutation-positive cohort, the majority being defects in the right side of the heart. The most common facial features were downward-slanting palpebral fissures, hypertelorism and low-set posteriorly rotated ears. Other clinical features included short stature (40%), pectus excavatum (54%) and, in males, unilateral or bilateral cryptorchidism (44%). CONCLUSION The clinical features and mutational spectrum observed in our cohort are similar to those reported in other large studies done worldwide. This is the largest case series of NS-affected individuals with PTPN11 mutations described till date from India.

中文翻译：

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107种Noonan综合征的分子和临床研究影响了PTPN11突变的个体。

背景技术Noonan综合征（NS）是一种常染色体显性发育遗传疾病，由与RAS /丝裂原活化蛋白激酶（MAPK）途径相关的基因的种系突变引起。在一些研究中，PTPN11是受NS影响的患者中具有大量致病变异的基因之一。因此，在研究基因型-表型相关性之前，首先对临床诊断的NS个体进行PTPN11基因致病性变异测试，以确认其相关性。方法招募了来自印度南部四家医院的363名临床诊断为NS的个体，并对PTPN11基因的外显子进行了测序。结果在107例患者中检测到32个先前描述的PTPN11基因八个外显子中的病原体变异，其中10例为家族性病例。外显子3 8和13具有最高的致病变异体数。该系列中最常见的致病变异是在第8外显子中（c.922A> G，c.923A> G），在22位受影响的患者中观察到。先天性心脏异常存在于84％的突变阳性人群中，其中大多数是心脏右侧的缺陷。最常见的面部特征是向下倾斜的睑裂，过度伸缩和低位向后旋转耳朵。其他临床特征还包括身材矮小（40％），胸腔直肠切除（54％），以及男性单侧或双侧隐睾症（44％）。结论在我们的队列中观察到的临床特征和突变谱与在全球范围内进行的其他大型研究中报道的相似。