Scopus
🔓 Açık Erişim YÖKSİS Eşleşti
Comprehensive genetic analysis of RASopathy in the era of next-generation sequencing and definition of a novel likely pathogenic KRAS variation
Molecular Syndromology · Ocak 2022
YÖKSİS Kayıtları
COMPREHENSIVE GENETIC ANALYSIS OF RASOPATHY IN THE ERA OF NEXT-GENERATION SEQUENCING AND DEFINITION OF A NOVEL LIKELY PATHOGENIC KRAS VARIATION
MOLECULAR SYNDROMOLOGY · 2022 SCI-Expanded
DOKTOR ÖĞRETİM ÜYESİ FATMA ÖZGÜÇ ÇÖMLEK →
Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variation
Molecular Syndromology · 2022 SCI-Expanded
PROFESÖR RAMAZAN YILDIRIM →
Makale Bilgileri
DergiMolecular Syndromology
Yayın TarihiOcak 2022
Cilt / Sayfa13 · 88-98
Scopus ID2-s2.0-85123517987
Erişim🔓 Açık Erişim
Özet
Introduction: Germline pathogenic variations of the genes encoding the components of the Ras-MAPK pathway are found to be responsible for RASopathies, a clinically and genetically heterogeneous group of diseases. In this study, we aimed to present the results of patients genetically investigated for RASopathy-related mutations in our Genetic Diagnosis Center. Methods: The results of 51 unrelated probands with RASopathy and 4 affected relatives (31 male, 24 female; mean age: 9.327 ± 8.214) were included in this study. Mutation screening was performed on DNA samples from peripheral blood of the patients either by Sanger sequencing of PTPN11 hotspot regions (10/51 probands), or by a targeted amplicon next-generation sequencing panel (41/51 probands) covering the exonic regions of BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, RASA2, RIT1, SHOC2, SOS1, SOS2, SPRED1, and KAT6B genes. Results: Pathogenic/likely pathogenic variations found in 22 out of 51 probands (43.13%) and their 4 affected family members were located in PTPN11, BRAF, KRAS, NF1, RAF1, SOS1, and SHOC2 genes. The c.148A>C (p.Thr50Pro) variation in the KRAS gene was a novel variant detected in a sibling in our patient cohort. We found supportive evidence for the pathogenicity of the NF1 gene c.5606G>T (p.Gly1869Val) variation which we defined in an affected boy who inherited the mutation from his affected father. Conclusion: Although PTPN11 is the most frequently mutated gene in our patient cohort, as in most previous reports, different mutation distribution among the other genes studied motivates the use of a nextgeneration sequencing gene panel including the possible responsible genes.
Yazarlar (12)
1
Selma Demir
2
Hümeyra Yaşar Köstek
ORCID: 0000-0003-4268-3535
3
Aslihan Sanri
4
Ruken Yildirim
5
Fatma Özgüç Çömlek
ORCID: 0000-0002-2752-3480
6
Sinem Yalçintepe
7
Murat Deveci
8
Emine Ikbal Atli
9
Engin Atli
10
Damla Eker
11
Hakan Gürkan
ORCID: 0000-0002-8967-6124
12
Filiz Tütüncüler Kökenli
ORCID: 0000-0003-3710-288X
Anahtar Kelimeler
KRAS
Next-generation sequencing
RASopathy
Kurumlar
Diyarbakir Pediatric Diseases Hospital
Diyarbakir Turkey
Ondokuz Mayis University, Medical School
Samsun Turkey
Trakya University, Faculty of Medicine
Edirne Turkey
Metrikler
1
Atıf
12
Yazar
3
Anahtar Kelime