NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy. Issue 5 (11th February 2018)

• Record Type: Journal Article
• Authors: Ishiyama, A.; Muramatsu, K.; Uchino, S.; Sakai, C.; Matsushima, Y.; Makioka, N.; Ogata, T.; Suzuki, E.; Komaki, H.; Sasaki, M.; Mimaki, M.; Goto, Y.‐I.; Nishino, I.
• Is Part Of: Clinical genetics. Volume 93:Issue 5(2018)
• Page Start: 1103
• Page End: 1106
• Publication Date: 2018-02-11
• Subjects: assembly factor -- 2D‐BN‐PAGE/SDS‐PAGE -- mitochondrial complex I -- NDUFAF3 -- respiratory enzyme activity; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13215
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1‐year‐old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two‐dimensional, blue‐native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate‐PAGE revealed reductions in Q‐module (NDUFS2, NDUFS3, and NDUFA9) and P‐module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3 . Abstract : Cavitating leukoencephalopathy