University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype

    Thumbnail
    Download
    Published version (3.307Mb)

    Citations
    Scopus
    Altmetric
    14
    Author
    Alston, CL; Howard, C; Olahova, M; Hardy, SA; He, L; Murray, PG; O'Sullivan, S; Doherty, G; Shield, JPH; Hargreaves, IP; ...
    Date
    2016-09-01
    Source Title
    Journal of Medical Genetics
    Publisher
    BMJ PUBLISHING GROUP
    University of Melbourne Author/s
    Thorburn, David
    Affiliation
    Paediatrics (RCH)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Alston, 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.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259277
    DOI
    10.1136/jmedgenet-2015-103576
    Abstract
    BACKGROUND: 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.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [52369]
    • Paediatrics (RCH) - Research Publications [2382]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors