Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosome is not involved in Rett syndrome

Am J Hum Genet. 1995 Mar;56(3):647-53.


Rett syndrome (RS), a progressive encephalopathy with onset in infancy, has been attributed to an X-linked mutation, mainly on the basis of its occurrence almost exclusively in females and its concordance in female MZ twins. The underlying mechanisms proposed are an X-linked dominant mutation with male lethality, uniparental disomy of the X chromosome, and/or some disturbance in the process of X inactivation leading to unequal distributions of cells expressing maternal or paternal alleles (referred to as a "nonrandom" or "skewed" pattern of X inactivation). To determine if the X chromosome is in fact involved in RS, we studied a group of affected females including three pairs of MZ twins, two concordant for RS and one uniquely discordant for RS. Analysis of X-inactivation patterns confirms the frequent nonrandom X inactivation previously observed in MZ twins but indicates that this is independent of RS. Analysis of 29 RS females reveals not one instance of uniparental X disomy, extending the observations previously reported. Therefore, our findings contribute no support for the hypothesis that RS is an X-linked disorder. Furthermore, the concordant phenotype in most MZ female twins with RS, which has not been observed in female twins with known X-linked mutations, argues against an X mutation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Twin Study

MeSH terms

  • Child
  • Chromosome Aberrations*
  • Diseases in Twins / genetics*
  • Dosage Compensation, Genetic*
  • Female
  • Genetic Linkage
  • Genotype
  • Humans
  • Pedigree
  • Rett Syndrome / genetics*
  • Twins, Monozygotic
  • X Chromosome*