Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease
| Autor: | Richard J. Rodenburg, Lindi-Maryn Jonck, Roan Louw, Etresia van Dyk, Maryke Schoonen, Francois H. van der Westhuizen, Izelle Smuts, Joanna L. Elson |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Mitochondrial DNA Mitochondrial Diseases Mitochondrial disease Population DNA Mitochondrial DNA sequencing Pathology and Forensic Medicine Cohort Studies Electron Transport 03 medical and health sciences 0302 clinical medicine Ethnicity medicine Humans SURF1 Child education Cell Nucleus Genetics education.field_of_study business.industry High-Throughput Nucleotide Sequencing Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] medicine.disease Mitochondria Nuclear DNA 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cohort Molecular Medicine Female business Cohort study |
| Zdroj: | Journal of Molecular Diagnostics, 21, 503-513 Journal of Molecular Diagnostics, 21, 3, pp. 503-513 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2019.02.002 |
| Popis: | Contains fulltext : 204158.pdf (Publisher’s version ) (Closed access) Mitochondrial disease (MD) is a group of rare inherited disorders with clinical heterogeneous phenotypes. Recent advances in next-generation sequencing (NGS) allow for rapid genetic diagnostics in patients who experience MD, resulting in significant strides in determining its etiology. This, however, has not been the case in many patient populations. We report on a molecular diagnostic study using mitochondrial DNA and targeted nuclear DNA (nDNA) NGS of an extensive cohort of predominantly sub-Saharan African pediatric patients with clinical and biochemically defined MD. Patients in this novel cohort presented mostly with muscle involvement (73%). Of the original 212 patients, a muscle respiratory chain deficiency was identified in 127 cases. Genetic analyses were conducted for these 127 cases based on biochemical deficiencies, for both mitochondrial (n = 123) and nDNA using panel-based NGS (n = 86). As a pilot investigation, whole-exome sequencing was performed in a subset of African patients (n = 8). These analyses resulted in the identification of a previously reported pathogenic mitochondrial DNA variant and seven pathogenic or likely pathogenic nDNA variants (ETFDH, SURF1, COQ6, RYR1, STAC3, ALAS2, and TRIOBP), most of which were identified via whole-exome sequencing. This study contributes to knowledge of MD etiology in an understudied, ethnically diverse population; highlights inconsistencies in genotype-phenotype correlations; and proposes future directions for diagnostic approaches in such patient populations. |
| Databáze: | OpenAIRE |
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