The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum

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dc.authoridÖZDEMİR, TAHA RESID/0000-0003-4870-6945
dc.authoridTekin, Hande Gazeteci/0000-0002-4407-164X
dc.authoridAdebali, Ogun/0000-0001-9213-4070
dc.authoridKöse, Melis/0000-0003-2255-3725
dc.authorwosidAykut, Ayca/B-1698-2018
dc.authorwosidÖZDEMİR, TAHA RESID/I-6761-2015
dc.authorwosidYILMAZ, ÜNSAL/ABG-7549-2021
dc.authorwosidTekin, Hande Gazeteci/AAV-4674-2021
dc.authorwosidkose, engin/W-4903-2017
dc.authorwosidAtik, Tahir/AAY-5682-2021
dc.authorwosidAdebali, Ogun/N-4159-2016
dc.contributor.authorKose, Melis
dc.contributor.authorIsik, Esra
dc.contributor.authorAykut, Ayca
dc.contributor.authorDurmaz, Asude
dc.contributor.authorKose, Engin
dc.contributor.authorErsoy, Melike
dc.contributor.authorDiniz, Gulden
dc.date.accessioned2023-01-12T20:10:55Z
dc.date.available2023-01-12T20:10:55Z
dc.date.issued2021
dc.departmentN/A/Departmenten_US
dc.description.abstractObjectives: Diagnostic process of mitochondrial disorders (MD) is challenging because of the clinical variability and genetic heterogeneity of these conditions. Next-Generation Sequencing (NGS) technology offers a high-throughput platform for nuclear MD. Methods: We included 59 of 72 patients that undergone WES and targeted exome sequencing panel suspected to have potential PMDs. Patients who were included in the analysis considering the possible PMD were reviewed retrospectively and scored according to the Mitochondrial Disease Criteria Scale. Results: Sixty-one percent of the patients were diagnosed with whole-exome sequencing (WES) (36/59) and 15% with targeted exome sequencing (TES) (9/59). Patients with MD-related gene defects were included in the mito group, patients without MD-related gene defects were included in the nonmito group, and patients in whom no etiological cause could be identified were included in the unknown etiology group. In 11 out of 36 patients diagnosed with WES, a TES panel was applied prior to WES. In 47 probands in 39 genes (SURF1, SDHAF1, MTO1, FBXL4, SLC25A12, GLRX5, C19oRF12, NDUFAF6, DARS2, BOLA3, SLC19A3, SCO1, HIBCH, PDHA1, PDHAX, PC, ETFA, TRMU, TUFM, NDUFS6, WWOX, UBCD TREX1, ATL1, VAC14, GFAP, PLA2G6, TPRKB, ATP8A2, PEX13, IGHMBP2, LAMB2, LPIN1, GFPT1, CLN5, DOLK) (20 mito group, 19 nonmito group) 59 variants (31 mito group, 18 nonmito group) were detected. Seven novel variants in the mito group (SLC25A12, GLRX5, DARS2, SCO1, PC, ETFA, NDUFS6), nine novel variants in the nonmito group (IVD, GCDH, COG4, VAC14, GFAP, PLA2G6, ATP8A2, PEX13, LPIN1) were detected. Conclusions: We explored the feasibility of identifying pathogenic alleles using WES and TES in MD. Our results show that WES is the primary method of choice in the diagnosis of MD until at least all genes responsible for PMD are found and are highly effective in facilitating the diagnosis process.en_US
dc.identifier.doi10.1515/jpem-2020-0410
dc.identifier.endpage430en_US
dc.identifier.issn0334-018X
dc.identifier.issn2191-0251
dc.identifier.issue4en_US
dc.identifier.pmid33629572en_US
dc.identifier.startpage417en_US
dc.identifier.urihttps://doi.org/10.1515/jpem-2020-0410
dc.identifier.urihttps://hdl.handle.net/11454/77977
dc.identifier.volume34en_US
dc.identifier.wosWOS:000637286800001en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWalter De Gruyter Gmbhen_US
dc.relation.ispartofJournal of Pediatric Endocrinology & Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectLeigh syndromeen_US
dc.subjectMendelian mitochondrial disorderen_US
dc.subjectnext-generation sequencingen_US
dc.subjectnuclear mitochondrial disordersen_US
dc.subjectwhole exome sequencingen_US
dc.titleThe utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrumen_US
dc.typeArticleen_US

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