[Symptomatic carriers of dystrophinopathy with chromosome X inactivation bias].
Several studies have recently highlighted the fact that the clinical involvement in females carrying a mutation in the dystrophin gene could be more frequent than usually thought, suggesting the need of a careful cardiac follow-up. Except for the classical chromosomal rearrangements, it was shown that a bias in the X chromosome inactivation process could be found in some affected females. We report two families illustrating different situations. The propositus of the first family, aged 32, presented with a proximal muscular weakness, increasing for three years, as well as elevated muscular enzymes in blood. Her brother suffered from classical Duchenne muscular dystrophy. Her mother was more severely affected, whereas her sister remained asymptomatic. A duplication of exons 3 to 7 of the dystrophin gene was found in all four patients. The affected carrier from the second family was a sporadic case. She has been suffering from proximal muscular weakness for six years. Muscle biopsy showed a mosaic pattern of the immunostaining using specific antidystrophin antibodies. A stop mutation was found in exon 52. Her ten year-old daughter, carrying the mutation, was asymptomatic. In both families, the inactivation profiles were in accordance with the clinical presentation. We discuss the different mechanisms that may lead to the inactivation bias in these patients, as well as the advantage and limits of using the X chromosome inactivation test as a tool for diagnosis and prognosis purpose in symptomatic carriers for dystrophinopathies.
D000293:Adolescent; D000328:Adult; D041321:Chromosomes, Human, X / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D020868:Gene Silencing; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics; D010375:Pedigree
D018388:Codon, Terminator; D016189:Dystrophin
Les conductrices symptomatiques pour les dystrophinopathies avec biais d'inactivation du chromosome X.