Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia

Neurogenetics. 2009 Oct;10(4):337-45. doi: 10.1007/s10048-009-0194-0. Epub 2009 May 21.

Abstract

Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Asian People / genetics
  • Base Sequence
  • Brain / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Dystonia / genetics*
  • Dystonia / pathology
  • Dystonia / physiopathology
  • Electron Transport Complex I / genetics*
  • Eye / pathology
  • Female
  • Genes, Mitochondrial*
  • Humans
  • Leigh Disease / genetics
  • Male
  • Molecular Sequence Data
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Optic Atrophy, Hereditary, Leber / pathology
  • Optic Atrophy, Hereditary, Leber / physiopathology
  • Pedigree
  • Point Mutation*
  • Polymorphism, Genetic
  • Young Adult

Substances

  • Electron Transport Complex I
  • MT-ND3 protein, human