Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variation

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dc.authoridDeveci, Murat/0000-0001-6246-671X
dc.authoridGürkan, Hakan/0000-0002-8967-6124
dc.authoridÖzgüç Çömlek, Fatma/0000-0002-2752-3480
dc.authoridatli, emine ikbal/0000-0001-9003-1449
dc.authoridDemir, Selma/0000-0002-0964-5513
dc.authorwosidDeveci, Murat/A-6913-2015
dc.authorwosidyildirim, ruken/G-8137-2018
dc.authorwosidGürkan, Hakan/AAF-2866-2020
dc.authorwosidÖzgüç Çömlek, Fatma/ABS-9242-2022
dc.authorwosidatli, emine ikbal/AAN-5060-2020
dc.authorwosidSANRI, ASLiHAN/ADL-6838-2022
dc.authorwosidDemir, Selma/A-1500-2018
dc.contributor.authorDemir, Selma
dc.contributor.authorKostek, Huemeyra Yasar
dc.contributor.authorSanri, Aslihan
dc.contributor.authorYildirim, Ruken
dc.contributor.authorComlek, Fatma Oezguec
dc.contributor.authorYalcintepe, Sinem
dc.contributor.authorDeveci, Murat
dc.date.accessioned2024-06-12T11:13:23Z
dc.date.available2024-06-12T11:13:23Z
dc.date.issued2022
dc.departmentTrakya Üniversitesien_US
dc.description.abstractIntroduction: 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 next-generation sequencing gene panel including the possible responsible genes.en_US
dc.identifier.doi10.1159/000520722
dc.identifier.issn1661-8769
dc.identifier.issn1661-8777
dc.identifier.pmid35418823en_US
dc.identifier.scopus2-s2.0-85123517987en_US
dc.identifier.scopusqualityQ4en_US
dc.identifier.urihttps://doi.org/10.1159/000520722
dc.identifier.urihttps://hdl.handle.net/20.500.14551/23532
dc.identifier.wosWOS:000740844200001en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherKargeren_US
dc.relation.ispartofMolecular Syndromologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectRasopathyen_US
dc.subjectKRASen_US
dc.subjectNext-Generation Sequencingen_US
dc.subjectNoonan-Syndromeen_US
dc.subjectPhenotypeen_US
dc.subjectMutationsen_US
dc.subjectSpectrumen_US
dc.titleComprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variationen_US
dc.typeArticleen_US

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