Symptoms in Carriers of Adrenoleukodystrophy Relate to Skewed X Inactivation

Ann Neurol. 2002 Nov;52(5):683-8. doi: 10.1002/ana.10376.

Abstract

Skewing of X inactivation may contribute to the manifestation of symptoms in adrenoleukodystrophy carriers. We observed highly skewed X inactivation in 32% of 22 symptomatic and asymptomatic carriers but not in 7 related and 35 unrelated controls. Skewing of X inactivation correlated with clinical neurological scores but not with the extent of very long-chain fatty acid accumulation. Transcript analysis in cultured fibroblasts revealed that skewing could occur both in favor of the mutant and the wild-type allele. Adrenoleukodystrophy carriers are more susceptible to develop skewing of X inactivation in favor of the mutant allele being associated with the manifestation of symptoms.

MeSH terms

  • Adolescent
  • Adrenoleukodystrophy / blood
  • Adrenoleukodystrophy / genetics*
  • Adrenoleukodystrophy / physiopathology
  • Adult
  • Child, Preschool
  • Fatty Acids / blood
  • Fatty Acids / chemistry
  • Female
  • Fibroblasts / physiology
  • Heterozygote*
  • Humans
  • Middle Aged
  • Reference Values
  • Sex Chromosome Aberrations*
  • Transcription, Genetic
  • X Chromosome*

Substances

  • Fatty Acids