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The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum.
Kose, Melis; Isik, Esra; Aykut, Ayça; Durmaz, Asude; Kose, Engin; Ersoy, Melike; Diniz, Gulden; Adebali, Ogun; Ünalp, Aycan; Yilmaz, Ünsal; Karaoglu, Pakize; Edizer, Selvinaz; Tekin, Hande Gazeteci; Özdemir, Taha Resid; Atik, Tahir; Onay, Hüseyin; Özkinay, Ferda.
Afiliación
  • Kose M; Department of Pediatrics, Division of Inborn Errors of Metabolism, Izmir Katip Çelebi University, Izmir, Turkey.
  • Isik E; Department of Pediatrics, Division of Genetics, Ege University, Izmir, Turkey.
  • Aykut A; Department of Pediatrics, Division of Genetics, Ege University, Izmir, Turkey.
  • Durmaz A; Department of Medical Genetics, Ege University, Izmir, Turkey.
  • Kose E; Department of Medical Genetics, Ege University, Izmir, Turkey.
  • Ersoy M; Department of Pediatrics, Division of Inborn Errors of Metabolism, Ankara University, Ankara, Turkey.
  • Diniz G; Department of Pediatrics, Division of Inborn Errors of Metabolism, Health Sciences University, Bakirkoy Sadi Konuk Research and Training Hospital, Istanbul, Turkey.
  • Adebali O; Department of Pathology, Izmir Democrasy University, Izmir, Turkey.
  • Ünalp A; Adebali Lab, Molecular Biology, Genetics and Bioengineering Program, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
  • Yilmaz Ü; Department of Pediatric Neurology, Health Sciences University Dr. Behçet Uz Children Research and Training Hospital, Izmir, Turkey.
  • Karaoglu P; Department of Pediatric Neurology, Health Sciences University Dr. Behçet Uz Children Research and Training Hospital, Izmir, Turkey.
  • Edizer S; Department of Pediatric Neurology, Health Sciences University Dr. Behçet Uz Children Research and Training Hospital, Izmir, Turkey.
  • Tekin HG; Department of Pediatrics, Division of Pediatric Neurology, Kanuni Sultan Suleyman University, Istanbul, Turkey.
  • Özdemir TR; Department of Pediatrics, Division of Pediatric Neurology, Çigli Training and Research Hospital, Izmir, Turkey.
  • Atik T; Department of Medical Genetics, Health Sciences University Tepecik Training and Research Hospital, Izmir, Turkey.
  • Onay H; Department of Pediatrics, Division of Genetics, Ege University, Izmir, Turkey.
  • Özkinay F; Department of Medical Genetics, Ege University, Izmir, Turkey.
J Pediatr Endocrinol Metab ; 34(4): 417-430, 2021 Apr 27.
Article en En | MEDLINE | ID: mdl-33629572
OBJECTIVES: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Mitocondriales / Secuenciación de Nucleótidos de Alto Rendimiento / Secuenciación del Exoma Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: J Pediatr Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / PEDIATRIA Año: 2021 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Mitocondriales / Secuenciación de Nucleótidos de Alto Rendimiento / Secuenciación del Exoma Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: J Pediatr Endocrinol Metab Asunto de la revista: ENDOCRINOLOGIA / PEDIATRIA Año: 2021 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Alemania