NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy

A. Ishiyama, K. Muramatsu, S. Uchino, C. Sakai, Y. Matsushima, N. Makioka, T. Ogata, E. Suzuki, H. Komaki, M. Sasaki, M. Mimaki, Y. I. Goto, I. Nishino

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1103-1106
Number of pages4
JournalClinical Genetics
Volume93
Issue number5
DOIs
Publication statusPublished - May 2018

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Leukoencephalopathies
Basal Ganglia
Lactic Acid
Exome
Mediodorsal Thalamic Nucleus
Native Polyacrylamide Gel Electrophoresis
Corpus Callosum
Substantia Nigra
Consciousness
Sodium Dodecyl Sulfate
Respiratory Tract Infections
Polyacrylamide Gel Electrophoresis
Skeletal Muscle
Magnetic Resonance Spectroscopy
Phenotype
Brain
Enzymes
White Matter

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy. / 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.

In: Clinical Genetics, Vol. 93, No. 5, 05.2018, p. 1103-1106.

Research output: Contribution to journalArticle

Ishiyama, A, Muramatsu, K, Uchino, S, Sakai, C, Matsushima, Y, Makioka, N, Ogata, T, Suzuki, E, Komaki, H, Sasaki, M, Mimaki, M, Goto, YI & Nishino, I 2018, 'NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy', Clinical Genetics, vol. 93, no. 5, pp. 1103-1106. https://doi.org/10.1111/cge.13215
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. / NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy. In: Clinical Genetics. 2018 ; Vol. 93, No. 5. pp. 1103-1106.
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