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Ann Neurol. 2019 Aug;86(2):310-315. doi: 10.1002/ana.25525. Epub 2019 Jul 1.

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

Author information

1
Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
2
Faculty of Medicine, University of Turku, and Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
3
Medical Research Council Centre for Neuromuscular Diseases, University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom.
4
Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, London, United Kingdom.
5
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom.
6
Royal Manchester Children's Hospital, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester, United Kingdom.
7
Department of Paediatric Neurology, Royal Preston Hospital, Preston, United Kingdom.
8
South West Thames Regional Genetics Service, St. George's Hospital, London, United Kingdom.
9
Alder Hey Children's National Health Service Foundation Trust, Liverpool, United Kingdom.
10
Greater Glasgow and Clyde National Health Service Yorkhill Hospital, Glasgow, United Kingdom.
11
Greater Manchester Neuroscience Centre, Salford Royal National Health Service Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom.
12
Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
13
Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
14
MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom.
15
Department of Paediatrics, The Children's Hospital, Oxford, United Kingdom.
16
Oxford Medical Genetics Laboratories, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom.

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;86:310-315.

PMID:
31187502
DOI:
10.1002/ana.25525

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