Symptoms in carriers of adrenoleukodystrophy relate to skewed X inactivation.
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.
Maier
Esther M
EM
Laboratory of Molecular Biology, Dr von Hauner Children's Hospital, University of Munich, Lindwurmstrasse 4, 80337 Munich, Germany.
Kammerer
Stefan
S
Muntau
Ania C
AC
Wichers
Maria
M
Braun
Andreas
A
Roscher
Adelbert A
AA
D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D002675:Child, Preschool; D005227:Fatty Acids / Q000097:blood / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D012729:Sex Chromosome Aberrations; D014158:Transcription, Genetic; D014960:X Chromosome
D005227:Fatty Acids