Pathogenic variants in MT-ATP6: A United Kingdom-based mitochondrial disease cohort study.

TitlePathogenic variants in MT-ATP6: A United Kingdom-based mitochondrial disease cohort study.
Publication TypeJournal Article
Year of Publication2019
AuthorsNg, YShiau, Martikainen, MH, Gorman, GS, Blain, A, Bugiardini, E, Bunting, A, Schaefer, AM, Alston, CL, Blakely, EL, Sharma, S, Hughes, I, Lim, A, de Goede, C, McEntagart, M, Spinty, S, Horrocks, I, Roberts, M, Woodward, CE, Chinnery, PF, Horvath, R, Nesbitt, V, Fratter, C, Poulton, J, Hanna, MG, Pitceathly, RDS, Taylor, RW, Turnbull, DM, McFarland, R
JournalAnn Neurol
Date Published2019 Jun 11
ISSN1531-8249
Abstract

Distinct clinical syndromes have been associated with pathogenic MT-ATP6 variants. In this cohort study, we identified 125 individuals (60 families) including 88 clinically affected individuals and 37 asymptomatic carriers. Thirty-one individuals presented with Leigh syndrome and 7 with neuropathy ataxia retinitis pigmentosa. The remaining 50 patients presented with variable nonsyndromic features including ataxia, neuropathy, and learning disability. We confirmed maternal inheritance in 39 families and demonstrated that tissue segregation patterns and phenotypic threshold are variant dependent. Our findings suggest that MT-ATP6-related mitochondrial DNA disease is best conceptualized as a mitochondrial disease spectrum disorder and should be routinely included in genetic ataxia and neuropathy gene panels. ANN NEUROL 2019.

DOI10.1002/ana.25525
Alternate JournalAnn. Neurol.
Citation Key10.1002/ana.25525
PubMed ID31187502
Grant List / / Biotechnology and Biological Sciences Research Council /
309548 / / H2020 European Research Council /
G0601943 / / Medical Research Council / United Kingdom
L016354 / / Medical Research Council / United Kingdom
MC_UP_1501/2 / / Medical Research Council / United Kingdom
MR/K000608/1 / / Medical Research Council / United Kingdom
MR/N025431/1 / / Medical Research Council / United Kingdom
CL-2016-01-003 / / National Institute for Health Research /
NIHR-HCS-D12-03-04 / / National Institute for Health Research /
MR/N027302/1 / / Newton Fund /
/ / Sigrid Juséliuksen Säätiö /
/ / UK NHS Specialist Commissioners /
109915/Z/15/Z / / Wellcome Trust / United Kingdom
201064/Z/16/Z / / Wellcome Trust / United Kingdom
203105 / / Wellcome Trust / United Kingdom
212219/Z/18/Z / / Wellcome Trust / United Kingdom