X-linked mental retardation: evidence for a recent mutation in a five-generation family (MRX65) linked to the pericentromeric region

Am J Med Genet. 1999 Jul 30;85(3):305-8. doi: 10.1002/(sici)1096-8628(19990730)85:3<305::aid-ajmg22>3.0.co;2-5.


We report linkage analysis in a new family with nonspecific X-linked mental retardation, using 27 polymorphic markers covering the entire X-chromosome. We could assign the underlying disease gene, denoted MRX65, to the pericentromeric region, with flanking markers DXS573 in Xp11.3 and DXS990 in Xq21.33. A maximum LOD score of 3.64 was found at markers ALAS2 (Xp11.22) and DXS453 (Xq12) at straight theta = 0. Twenty-five of the 58 reported MRX families are linked to a region that is partially overlapping with the region reported here. Extension of the pedigree showed a number of unaffected distant relatives with haplotypes corresponding to the disease locus. Apparently, a new mutation in a female is causative for the disease in the family reported here. Furthermore, we show the importance of combining clinical, cytogenetic, and molecular studies since one of the family members, expected to be affected by the same genetic defect, has a 48,XXXY karyotype.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Weights and Measures
  • Centromere / genetics
  • Child
  • DNA / genetics
  • Family Health
  • Female
  • Genetic Linkage
  • Humans
  • Intellectual Disability / genetics*
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation
  • Pedigree
  • Psychiatric Status Rating Scales
  • Psychometrics
  • X Chromosome / genetics*


  • DNA