Toggle Main Menu Toggle Search

Open Access padlockePrints

The Newcastle University research output collection, currently available on ePrints, will shortly be moving to a new open repository platform, Figshare. To prepare for the data migration we have paused adding new content to ePrints, and will resume once the new repository is launched. During this time you will continue to have access to ePrints (but no new content will appear). We will share updates here when available.

The clinical spectrum of the m.10191T > C mutation in complex I-deficient Leigh syndrome

Lookup NU author(s): Dr Victoria Nesbitt, Dr Charlotte Alston, Professor Bobby McFarlandORCiD, Professor Robert TaylorORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Mitochondrial respiratory chain diseases represent one of the most common inherited neurometabolic disorders of childhood, affecting a minimum of 1 in 7500 live births. The marked clinical, biochemical, and genetic heterogeneity means that accurate genetic counselling relies heavily upon the identification of the underlying causative mutation in the individual and determination of carrier status in the parents. Isolated complex I deficiency is the most common respiratory chain defect observed in children, resulting in organ-specific or multisystem disease, but most often presenting as Leigh syndrome, for which mitochondrial DNA mutations are important causes. Several recurrent, pathogenic point mutations in the MTND3 gene including m.10191T>C (p.Ser45Pro) have been previously identified. In this short clinical review we evaluate the case reports of the m.10191T>C mutation causing complex I-deficient Leigh syndrome described in the literature, in addition to two new ones diagnosed in our laboratory. Both of these appear to have arisen de novo without transmission of the mutation from mother to offspring, illustrating the importance not only of fully characterizing the mitochondrial genome as part of the investigation of children with complex I-deficient Leigh syndrome but also of assessing maternal samples to provide crucial genetic advice for families.

Publication metadata

Author(s): Nesbitt V, Morrison PJ, Crushell E, Donnelly DE, Alston CL, He LP, Mcfarland R, Taylor RW

Publication type: Review

Publication status: Published

Journal: Developmental Medicine and Child Neurology

Year: 2012

Volume: 54

Issue: 6

Pages: 500-506

Print publication date: 27/02/2012

ISSN (print): 0012-1622

ISSN (electronic): 1469-8749

Publisher: WILEY-BLACKWELL

URL: http://dx.doi.org/10.1111/j.1469-8749.2012.04224.x

DOI: 10.1111/j.1469-8749.2012.04224.x

Share