Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations
Open Access
- 12 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Medical Genetics
- Vol. 21 (1), 1-10
- https://doi.org/10.1186/s12881-020-0986-5
Abstract
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. Individuals (363) with clinically diagnosed NS from four hospitals in South India were recruited and the exons of PTPN11 gene were sequenced. 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%). 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.Keywords
This publication has 70 references indexed in Scilit:
- Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short statureProceedings of the National Academy of Sciences of the United States of America, 2012
- Noonan syndrome and clinically related disordersBest Practice & Research Clinical Endocrinology & Metabolism, 2011
- Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like PhenotypeAmerican Journal of Human Genetics, 2010
- A restricted spectrum of NRAS mutations causes Noonan syndromeNature Genetics, 2009
- Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hairNature Genetics, 2009
- Genotype differences in cognitive functioning in Noonan syndromeGenes, Brain and Behavior, 2009
- Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformationProceedings of the National Academy of Sciences of the United States of America, 2009
- Germline gain-of-function mutations in SOS1 cause Noonan syndromeNature Genetics, 2006
- Germline KRAS mutations cause Noonan syndromeNature Genetics, 2006
- Germline mutations in HRAS proto-oncogene cause Costello syndromeNature Genetics, 2005