دورية أكاديمية

Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations

التفاصيل البيبلوغرافية
العنوان: Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations
المؤلفون: Jeevana Praharsha Athota, Meenakshi Bhat, Sheela Nampoothiri, Kalpana Gowrishankar, Sanjeeva Ghanti Narayanachar, Vinuth Puttamallesh, Mohammed Oomer Farooque, Swathi Shetty
المصدر: BMC Medical Genetics, Vol 21, Iss 1, Pp 1-10 (2020)
بيانات النشر: BMC, 2020.
سنة النشر: 2020
المجموعة: LCC:Internal medicine
LCC:Genetics
مصطلحات موضوعية: Noonan syndrome, PTPN11, Mutational analysis, Congenital heart defects, SHP-2, RASopathy, Internal medicine, RC31-1245, Genetics, QH426-470
الوصف: Abstract 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1471-2350
Relation: http://link.springer.com/article/10.1186/s12881-020-0986-5; https://doaj.org/toc/1471-2350
DOI: 10.1186/s12881-020-0986-5
URL الوصول: https://doaj.org/article/0a3340fdb8c0407ebe9bdd5128735d30
رقم الأكسشن: edsdoj.0a3340fdb8c0407ebe9bdd5128735d30
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14712350
DOI:10.1186/s12881-020-0986-5