Premium
Pathogenic variants in MT‐ATP6 : A United Kingdom–based mitochondrial disease cohort study
Author(s) -
Ng Yi Shiau,
Martikainen Mika H.,
Gorman Gráinne S.,
Blain Alasdair,
Bugiardini Enrico,
Bunting Apphia,
Schaefer Andrew M.,
Alston Charlotte L.,
Blakely Emma L.,
Sharma Sunil,
Hughes Imelda,
Lim Albert,
de Goede Christian,
McEntagart Meriel,
Spinty Stefan,
Horrocks Iain,
Roberts Mark,
Woodward Cathy E.,
Chinnery Patrick F.,
Horvath Rita,
Nesbitt Victoria,
Fratter Carl,
Poulton Joanna,
Hanna Michael G.,
Pitceathly Robert D. S.,
Taylor Robert W.,
Turnbull Doug M.,
McFarland Robert
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25525
Subject(s) - ataxia , mitochondrial dna , medicine , genetics , mitochondrial disease , cohort , asymptomatic carrier , disease , asymptomatic , retinitis pigmentosa , biology , gene , psychiatry
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;86:310–315