Panel-based nuclear and mitochondrial next-generation sequencing outcomes of an ethnically diverse pediatric patient cohort with mitochondrial disease

dc.contributor.authorSchoonen, Maryke
dc.contributor.authorSmuts, Izelle
dc.contributor.authorLouw, Roan
dc.contributor.authorElson, Joanna L.
dc.contributor.authorVan Dyk, Etresia
dc.contributor.authorJonck, Lindi-Maryn
dc.contributor.authorRodenburg, Richard J.T.
dc.contributor.authorVan der Westhuizen, Francois H.
dc.date.accessioned2019-10-25T07:05:13Z
dc.date.issued2019-05
dc.description.abstractMitochondrial 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.en_ZA
dc.description.departmentPaediatrics and Child Healthen_ZA
dc.description.embargo2020-05-01
dc.description.librarianhj2019en_ZA
dc.description.urihttps://jmd.amjpathol.orgen_ZA
dc.identifier.citationSchoonen, M., Smuts, I., Louw, R. et al. 2019, 'Panel-based nuclear and mitochondrial next-generation sequencing outcomes of an ethnically diverse pediatric patient cohort with mitochondrial disease', Journal of Molecular Diagnostics, vol. 21, no. 3, pp. 503-513.en_ZA
dc.identifier.issn1525-1578 (print)
dc.identifier.issn1943-7811 (online)
dc.identifier.other10.1016/j.jmoldx.2019.02.002
dc.identifier.urihttp://hdl.handle.net/2263/71997
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Journal of Molecular Diagnostics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Journal of Molecular Diagnostics, vol. 21, no. 3, pp. 503-513, 2019. doi : 10.1016/j.jmoldx.2019.02.002.en_ZA
dc.subjectMitochondrial disease (MD)en_ZA
dc.subjectNext-generation sequencing (NGS)en_ZA
dc.subjectNuclear DNA (nDNA)en_ZA
dc.subjectMitochondrial DNA (mtDNA)en_ZA
dc.subjectPediatric patienten_ZA
dc.titlePanel-based nuclear and mitochondrial next-generation sequencing outcomes of an ethnically diverse pediatric patient cohort with mitochondrial diseaseen_ZA
dc.typePostprint Articleen_ZA

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