In situ hybridization shows direct evidence of skewed X inactivation in one of monozygotic twin females manifesting Duchenne muscular dystrophy.
A novel combination of conventional and molecular cytogenetic techniques was used to investigate the expression of an X-linked recessive disorder in one of monozygotic (MZ) twin females. These twins carry a deletion, approximately 300 kb in length, in one of their X chromosomes within the dystrophin gene, which is responsible for Duchenne muscular dystrophy (DMD) in one twin [Richards et al.: Am J Hum Genet 46:672-681, 1990]. A unique DNA fragment generated from an exon within this gene deletion was hybridized in situ to both twins' metaphase chromosomes, a probe which would presumably hybridize only to the normal X chromosome and not to the X chromosome carrying the gene deletion. Chromosomes were identified by reverse-banding (R-banding) and by the addition of 5-bromodeoxyuridine (BrdU) in culture to distinguish early and late replicating X chromosomes, corresponding to active and inactive X chromosomes, respectively. Hybridization experiments showed predominant inactivation of the normal X chromosome in the twin with DMD. This is the first report showing direct evidence at the chromosome level of unequal inactivation of cytogenetically normal X chromosomes resulting in the manifestation of an X-linked recessive disorder in one of monozygotic twin females. This study may now facilitate other research of unequal X inactivation and of females manifesting X-linked recessive disorders.
Zneimer
S M
SM
University of Texas Southwestern Medical Center, Department of Pathology, Dallas.
Schneider
N R
NR
Richards
C S
CS
D002871:Chromosome Banding; D015342:DNA Probes; D004200:Diseases in Twins / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D016189:Dystrophin / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D017403:In Situ Hybridization; D009136:Muscular Dystrophies / Q000235:genetics*; D014430:Twins, Monozygotic
D015342:DNA Probes; D016189:Dystrophin