Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X

Am J Med Genet A. 2005 Sep 15;138(1):18-20. doi: 10.1002/ajmg.a.30901.


X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is a syndromic form of X-linked mental retardation. We investigated the X-inactivation status of nine female ATR-X carriers by methylation-specific PCR of the HUMARA gene. Six carriers demonstrated a skewed X-inactivation pattern (>90:10) and one showed a non-skewed pattern (72:28), while two were uninformative because of homozygosity for the CAG repeat polymorphic alleles in the HUMARA. Only the carrier mother who showed non-skewed X-inactivation had moderate mental retardation. These findings suggest that mutations in ATRX may cause mental retardation in females, if the X chromosome carrying mutated ATRX is not properly inactivated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X / genetics*
  • DNA Helicases / genetics*
  • DNA Methylation
  • Dosage Compensation, Genetic*
  • Female
  • Genetic Linkage
  • Heterozygote
  • Humans
  • Mental Retardation, X-Linked / genetics*
  • Mutation
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction / methods
  • Receptors, Androgen / genetics
  • X-linked Nuclear Protein
  • alpha-Thalassemia / genetics*


  • AR protein, human
  • Nuclear Proteins
  • Receptors, Androgen
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein

Associated data

  • OMIM/242860
  • OMIM/301040