Recessive mutations in NDUFA2 cause mitochondrial leukoencephalopathy. Issue 2 (21st December 2017)

• Record Type: Journal Article
• 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.
• Is Part Of: Clinical genetics. Volume 93:Issue 2(2018)
• Page Start: 396
• Page End: 400
• Publication Date: 2017-12-21
• Subjects: complex I deficiency -- leukodystrophy -- leukoencephalopathy -- NDUFA2 -- whole‐exome sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13126
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : 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 . Abstract :