New Mutations Associated with Rasopathies in a Central European Population and Genotype-Phenotype Correlations
- 26 November 2015
- journal article
- Published by Wiley in Annals of Human Genetics
- Vol. 80 (1), 50-62
- https://doi.org/10.1111/ahg.12140
Abstract
We performed the genetic analysis of Rasopathy syndromes in patients from Central European by direct sequencing followed by next generation sequencing of genes associated with Rasopathies. All 51 patients harboured the typical features of Rasopathy syndromes. Thirty-five mutations were identified in the examined patients (22 in PTPN11, two in SOS1, one in RIT1, one in SHOC2, two in HRAS, three in BRAF, two in MAP2K1 and two in the NF1 gene). Two of them (p.Gly392Glu in the BRAF gene and p.Gln164Lys in the MAP2K1 gene) were novel with a potentially pathogenic effect on the structure of these proteins. Statistically significant differences in the presence of pulmonary stenosis (63.64% vs. 23.81%, P = 0.013897) and cryptorchidism (76.47% vs. 30%, P = 0.040224) were identified as the result of comparison of the prevalence of phenotypic features in patients with the phenotype of Noonan syndrome and mutation in the PTPN11 gene, with the prevalence of the same features in patients without PTPN11 mutation. Cryptorchidism as a statistically significant feature in our patients with PTPN11 mutation was not reported as significant in other European countries (Germany, Italy and Greece). The majority of mutations were clustered in exons 3 (45.45%), 8 (22.73%), and 13 (22.73%) of the PTPN11 gene.Keywords
Funding Information
- Ministry of Health of the Slovak Republic (2012/21-UKBA-21)
- Comenius University in Slovakia (UK/130/2013, UK/416/2014)
This publication has 61 references indexed in Scilit:
- 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
- Genomic duplication of PTPN11 is an uncommon cause of Noonan syndromeAmerican Journal of Medical Genetics Part A, 2009
- Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hairNature Genetics, 2009
- Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndromeNature Genetics, 2006
- Germline gain-of-function mutations in SOS1 cause Noonan syndromeNature Genetics, 2006
- The cardiofaciocutaneous syndromeJournal of Medical Genetics, 2006
- The natural history of Noonan syndrome: a long-term follow-up studyArchives of Disease in Childhood, 2006
- Germline KRAS mutations cause Noonan syndromeNature Genetics, 2006
- Germline mutations in HRAS proto-oncogene cause Costello syndromeNature Genetics, 2005