Browse by author
Lookup NU author(s): Maria Wesolowska, Professor Grainne Gorman, Dr Charlotte Alston, Aleksandra Pajak, Dr Angela Pyle, Dr Langping He, Dr Helen GriffinORCiD, Professor Patrick Chinnery, Dr James Miller, Dr Andrew Schaefer, Professor Robert Taylor, Professor Robert Lightowlers, Professor Zofia Chrzanowska-LightowlersORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Background: Mitochondrial disease can present at any age, with dysfunction in almost any tissue making diagnosis a challenge. It can result from inherited or sporadic mutations in either the mitochondrial or the nuclear genome, many of which affect intraorganellar gene expression. The estimated prevalence of 1/4300 indicates these to be amongst the commonest inherited neuromuscular disorders, emphasising the importance of recognition of the diagnostic clinical features. Objective: Despite major advances in our understanding of the molecular basis of mitochondrial diseases, accurate and early diagnoses are critically dependent on the fastidious clinical and biochemical characterisation of patients. Here we describe a patient harbouring a previously reported homozygous mutation in C12orf65, a mitochondrial protein of unknown function, which does not adhere to the proposed distinct genotype-phenotype relationship. Methods: We performed clinical, biochemical and molecular analysis including whole exome sequencing on patient samples and cell lines. Results: We report an extremely rare case of an adult presenting with Leigh-like disease, in intensive care, in the 5th decade of life, harbouring a recessively inherited mutation previously reported in children. A global reduction in intra-mitochondrial protein synthesis was observed despite normal or elevated levels of mt-RNA, leading to an isolated complex IV deficiency. Conclusions: All the reported C12orf65 mutations have shown an autosomal recessive pattern of inheritance. Mitochondrial disease causing mutations inherited in this manner are usually of early onset and associated with a severe, often fatal clinical phenotype. Presentations in adulthood are usually less severe. This patient's late adulthood presentation is in sharp contrast emphasising the clinical variability that is characteristic of mitochondrial disease and illustrates why making a definitive diagnosis remains a formidable challenge.
Author(s): Wesolowska M, Gorman GS, Alston CL, Pajak A, Pyle A, He L, Griffin H, Chinnery PF, Miller JAL, Schaefer AM, Taylor RW, Lightowlers RN, Chrzanowska-Lightowlers ZM
Publication type: Article
Publication status: Published
Journal: Journal of Neuromuscular Diseases
Year: 2015
Volume: 2
Issue: 4
Pages: 409-419
Print publication date: 01/10/2015
Acceptance date: 01/01/1900
Date deposited: 11/12/2017
ISSN (print): 2214-3599
ISSN (electronic): 2214-3602
Publisher: IOS Press
URL: https://doi.org/10.3233/JND-150121
DOI: 10.3233/JND-150121
Altmetrics provided by Altmetric
