Clinical and molecular findings in children with complex I deficiency

M. Bugiani, F. Invernizzi, S. Alberio, E. Briem, E. Lamantea, F. Carrara, I. Moroni, L. Farina, M. Spada, M. A. Donati, G. Uziel, M. Zeviani

Research output: Contribution to journalArticle

Abstract

Isolated complex I deficiency, the most frequent OXPHOS disorder in infants and children, is genetically heterogeneous. Mutations have been found in seven mitochondrial DNA (mtDNA) and eight nuclear DNA encoded subunits, respectively, but in most of the cases the genetic basis of the biochemical defect is unknown. We analyzed the entire mtDNA and 11 nuclear encoded complex I subunits in 23 isolated complex I-deficient children, classified into five clinical groups: Leigh syndrome, progressive leukoencephalopathy, neonatal cardiomyopathy, severe infantile lactic acidosis, and a miscellaneous group of unspecified encephalomyopathies. A genetic definition was reached in eight patients (35%). Mutations in mtDNA were found in six out of eight children with Leigh syndrome, indicating a prevalent association between this phenotype and abnormalities in ND genes. In two patients with leukoencephalopathy, homozygous mutations were detected in two different nuclear-encoded complex I genes, including a novel transition in NDUFS1 subunit. In addition to these, a child affected by mitochondrial encephalomyopathy had heterozygous mutations in NDUFA8 and NDUFS2 genes, while another child with neonatal cardiomyopathy had a complex rearrangement in a single NDUFS7 allele. The latter cases suggest the possibility of unconventional patterns of inheritance in complex I defects.

Original languageEnglish
Pages (from-to)136-147
Number of pages12
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1659
Issue number2-3
DOIs
Publication statusPublished - Dec 6 2004

Keywords

  • Children
  • Complex I deficiency
  • Mitochondrial disorder
  • mtDNA mutation
  • Nuclear DNA mutation

ASJC Scopus subject areas

  • Biophysics

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    Bugiani, M., Invernizzi, F., Alberio, S., Briem, E., Lamantea, E., Carrara, F., Moroni, I., Farina, L., Spada, M., Donati, M. A., Uziel, G., & Zeviani, M. (2004). Clinical and molecular findings in children with complex I deficiency. Biochimica et Biophysica Acta - Bioenergetics, 1659(2-3), 136-147. https://doi.org/10.1016/j.bbabio.2004.09.006