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

B. R. Migeon, M. A. Dunn, G. Thomas, B. J. Schmeckpeper, S. Naidu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)647-653
Number of pages7
JournalAmerican journal of human genetics
Volume56
Issue number3
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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