Highly skewed inactivation of the wild-type X-chromosome in asymptomatic female carriers of spinal and bulbar muscular atrophy (Kennedy's disease).
We examined families with a history of spinal and bulbar muscular atrophy (SBMA) and found that six out of eight female carriers had a skewed inactivation of the wild-type chromosome. Under these genetic conditions, disease manifestations should be expected and therefore we sought neurological and other symptoms of subclinical SBMA. We did not find either clinical symptoms or electrophysiological signs of mutated AR gene in female carriers, despite skewed methylation of the wild-type allele. These findings suggest that skewed methylation of AR genes are not necessarily associated to clinical manifestations in female carriers of the expanded SBMA allele.
Paradas
C
C
Servicio de Neurología del Hospital, Universitario Virgen de Valme, Seville, Spain.
Solano
F
F
Carrillo
F
F
Fernández
C
C
Bautista
J
J
Pintado
E
E
Lucas
M
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003402:Creatine Kinase / Q000032:analysis / Q000097:blood; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012727:Sex Characteristics; D012737:Sex Factors; D049951:X Chromosome Inactivation / Q000235:genetics*
D003402:Creatine Kinase