Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation.
Mitochondrial DNA disease is one of the most common groups of inherited neuromuscular disorders and frequently associated with marked phenotypic and genotypic heterogeneity. We describe an adult patient who initially presented with childhood-onset ataxia without a family history and an unremarkable diagnostic muscle biopsy. Subsequent multi-system manifestations included basal ganglia calcification, proteinuria, cataract and retinitis pigmentosa, prompting a repeat muscle biopsy that showed features consistent with mitochondrial myopathy 13 years later. She had a stroke with restricted diffusion change in the basal ganglia and internal capsule at age 44 years. Molecular genetic testing identified a previously-reported pathogenic, heteroplasmic mutation in the mitochondrial-encoded transfer RNA tryptophan (MT-TW) gene which based on family studies was likely to have arisen de novo in our patient. Interestingly, we documented an increase in the mutant mtDNA heteroplasmy level in her second biopsy (72% compared to 56%), reflecting the progression of clinical disease.
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Yi Shiau
YS
Ng
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Steven A
SA
Hardy
Nuffield Department of Obstetrics and Gynaecology, Women's Centre, Oxford, UK.
Venice
V
Shrier
Department of Neuroradiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Gerardine
G
Quaghebeur
Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
David R
DR
Mole
Division of Cardiovascular Medicine, BHF Oxbridge Centre of Regenerative Medicine, Oxford University, Oxford, UK.
Matthew J
MJ
Daniels
Oxford Eye Hospital, Oxford, UK.
Susan M
SM
Downes
Neurosciences Offices, Level 3 West Wing, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Jane
J
Freebody
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
Carl
C
Fratter
Neuropathology and Ocular Pathology Department, John Radcliffe Hospital, Oxford, UK.
Monika
M
Hofer
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Churchill Hospital, Oxford, UK.
Andrea H
AH
Nemeth
Nuffield Department of Obstetrics and Gynaecology, Women's Centre, Oxford, UK.
Joanna
J
Poulton
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. Electronic address: robert.taylor@ncl.ac.uk.
Robert W
RW
Taylor
D001259:Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging; D004272:DNA, Mitochondrial; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D010641:Phenotype
D004272:DNA, Mitochondrial
Ataxia; Mitochondrial DNA disease; Muscle biopsy; Proteinuria; Stroke