Recessive mutations in NDUFA2 cause mitochondrial leukoencephalopathy

Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report 2 patients with cystic leukoencephalopathy and complex I deficiency with recessive mut...

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Bibliographic Details
Published in:Clinical genetics 2018-02, Vol.93 (2), p.396-400
Main Authors: Perrier, S., Gauquelin, L., Tétreault, M., Tran, L.T., Webb, N., Srour, M., Mitchell, J.J., Brunel‐Guitton, C., Majewski, J., Long, V., Keller, S., Gambello, M.J., Simons, C., Vanderver, A., Bernard, G.
Format: Article
Language:English
Subjects:
Biochemical analysis
Carnitine
Child
Child, Preschool
complex I deficiency
Electron transport chain
Exome - genetics
Female
Genomes
Humans
Infant
Leigh Disease - genetics
Leigh Disease - physiopathology
leukodystrophy
Leukoencephalopathies - genetics
Leukoencephalopathies - physiopathology
Leukoencephalopathy
Male
Mitochondria
Mitochondria - genetics
Mitochondria - pathology
Mutation
NADH Dehydrogenase - genetics
NDUFA2
Patients
Solute Carrier Family 22 Member 5 - genetics
Whole Exome Sequencing
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Summary:Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report 2 patients with cystic leukoencephalopathy and complex I deficiency with recessive mutations in NDUFA2, an accessory subunit of complex I. The first patient was initially diagnosed with a primary systemic carnitine deficiency associated with a homozygous variant in SLC22A5, but also exhibited developmental regression and cystic leukoencephalopathy, and an additional diagnosis of complex I deficiency was suspected. Biochemical analysis confirmed a complex I deficiency, and whole‐exome sequencing revealed a homozygous mutation in NDUFA2 (c.134A>C, p.Lys45Thr). Review of a biorepository of patients with unsolved genetic leukoencephalopathies who underwent whole‐exome or genome sequencing allowed us to identify a second patient with compound heterozygous mutations in NDUFA2 (c.134A>C, p.Lys45Thr; c.225del, p.Asn76Metfs*4). Only 1 other patient with mutations in NDUFA2 and a different phenotype (Leigh syndrome) has previously been reported. This is the first report of cystic leukoencephalopathy caused by mutations in NDUFA2.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.13126