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dc.contributor.authorAlston, CL
dc.contributor.authorHoward, C
dc.contributor.authorOlahova, M
dc.contributor.authorHardy, SA
dc.contributor.authorHe, L
dc.contributor.authorMurray, PG
dc.contributor.authorO'Sullivan, S
dc.contributor.authorDoherty, G
dc.contributor.authorShield, JPH
dc.contributor.authorHargreaves, IP
dc.contributor.authorMonavari, AA
dc.contributor.authorKnerr, I
dc.contributor.authorMcCarthy, P
dc.contributor.authorMorris, AAM
dc.contributor.authorThorburn, DR
dc.contributor.authorProkisch, H
dc.contributor.authorClayton, PE
dc.contributor.authorMcFarland, R
dc.contributor.authorHughes, J
dc.contributor.authorCrushell, E
dc.contributor.authorTaylor, RW
dc.date.accessioned2021-02-04T01:09:12Z
dc.date.available2021-02-04T01:09:12Z
dc.date.issued2016-09-01
dc.identifierpii: jmedgenet-2015-103576
dc.identifier.citationAlston, C. L., Howard, C., Olahova, M., Hardy, S. A., He, L., Murray, P. G., O'Sullivan, S., Doherty, G., Shield, J. P. H., Hargreaves, I. P., Monavari, A. A., Knerr, I., McCarthy, P., Morris, A. A. M., Thorburn, D. R., Prokisch, H., Clayton, P. E., McFarland, R., Hughes, J. ,... Taylor, R. W. (2016). A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype. JOURNAL OF MEDICAL GENETICS, 53 (9), pp.634-641. https://doi.org/10.1136/jmedgenet-2015-103576.
dc.identifier.issn0022-2593
dc.identifier.urihttp://hdl.handle.net/11343/259277
dc.description.abstractBACKGROUND: Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. METHODS: Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. RESULTS: We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (<9th centile) and similar facial features including a prominent forehead, smooth philtrum and deep-set eyes associated with a recurrent homozygous c.64T>C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. CONCLUSIONS: Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features-particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry-should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations.
dc.languageEnglish
dc.publisherBMJ PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleA recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype
dc.typeJournal Article
dc.identifier.doi10.1136/jmedgenet-2015-103576
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleJournal of Medical Genetics
melbourne.source.volume53
melbourne.source.issue9
melbourne.source.pages634-641
dc.rights.licenseCC BY
melbourne.elementsid1054516
melbourne.contributor.authorThorburn, David
dc.identifier.eissn1468-6244
melbourne.accessrightsOpen Access


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