Wiskott-Aldrich syndrome carrier detection with the hypervariable marker M27 beta

Hum Genet. 1992 May;89(2):223-8. doi: 10.1007/BF00217127.

Abstract

Whole-blood cells of obligate carriers of the X-linked Wiskott-Aldrich syndrome (WAS) exhibit nonrandom inactivation of the X-chromosomes. However, because of the limited polymorphism of the probes available, the X-methylation pattern can only be determined in a restricted proportion of females. We thus analysed a large set of normal females and members of WAS families, using the recently described marker M27 beta, which detects the hyperpolymorphic locus DXS255. The probe was used to detect differences in methylation between the active and inactive X-chromosome, and the findings were compared with the pattern obtained using the well-documented probes from the 5' end of the PGK and HPRT genes. All the normal females were found to use either X-chromosome randomly, and there was complete correlation between the three probes in the populations studied. Segregation analysis performed with M27 beta and other related markers in the WAS families was fully in accordance with the X-inactivation data. The use of M27 beta, for both X-inactivation and segregation analysis of WAS kindreds, provides a basis for genetic counselling in the majority of families, including those with no surviving males.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Probes / genetics*
  • Dosage Compensation, Genetic*
  • Female
  • Genetic Carrier Screening
  • Genetic Markers / genetics
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Wiskott-Aldrich Syndrome / genetics*
  • X Chromosome*

Substances

  • DNA Probes
  • Genetic Markers