Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)(n) repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26)

T. H.M. Huang, J. F. Hejtmancik, A. Edwards, A. L. Pettigrew, C. A. Herrera, H. A. Hammond, C. T. Caskey, H. Y. Zoghbi, D. H. Ledbetter

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33 Scopus citations

Abstract

We recently reported a new X-linked mental retardation (XLMR) disorder in a four-generation family of Dutch descent. Features included Dandy-Walker malformation, basal ganglia disease, and seizures. Twenty-six family members, including two living affected males and two obligate carriers, were available for study. No evidence of linkage was observed between the disease locus and RFLPs from several X-chromosome regions, including Xp21-p22 (13 markers), proximal Xq (four markers), and Xq28 (three markers). However, a new hypervariable short tandem repeat (STR) within the HPRT gene at Xq26 showed positive linkage to the disease locus, with a maximum lod score of 2.19 at a recombination fraction of 0. A second hypervariable marker in Xq26, the dinucleotide repeat XL90A3 (DXS425), showed a lod score of .84 at a recombination fraction of .11. Both the HPRT and DXS425 markers were typed in 40 CEPH families, and subsequent multipoint linkage analysis showed the following order: Xcen-DXS425-(HPRT,XLMR)-F9-qter. HPRT and these flanking markers are therefore useful for carrier detection and prenatal diagnosis in this family. This study illustrates that hypervariable STRs will be powerful tools for linkage analysis and genetic diagnosis, particularly when relatively small families are involved.

Original languageEnglish (US)
Pages (from-to)1312-1319
Number of pages8
JournalAmerican Journal of Human Genetics
Volume49
Issue number6
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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