In situ hybridization shows direct evidence of skewed X inactivation in one of monozygotic twin females manifesting Duchenne muscular dystrophy

S. M. Zneimer, N. R. Schneider, C. S. Richards

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)601-605
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume45
Issue number5
DOIs
StatePublished - Jan 1 1993

Keywords

  • X chromosome
  • dystrophin gene
  • recessive disorder

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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