FURTHER LINKAGE EVIDENCE FOR LOCALIZATION OF MUTATIONAL SITES FOR NONSYNDROMIC TYPES OF X-LINKED MENTAL-RETARDATION AT THE PERICENTROMERIC REGION

We used several microsatellite markers scattered along the X chromosom e to search for linkage relationships in a large Sardinian pedigree se gregating for nonspecific X-linked mental retardation (MRX). Markers D XS573 and AR, located at chromosomal subregions Xp11.4-p11.22 and Xq11 .2-q12, respectively, were found to segregate in full concordance with the disease, leading to a LOD score of 4.21 at zero recombination val ue, Recombination with the disease was found with markers MAOB and DXS 454 located at Xp11.4-p11.3 and Xq21.1-q22, respectively; accordingly, markers distal to Xp11.4 and Xq22 also segregated independently of th e disease. These findings provide strong linkage evidence in favor of the localization of one MRX mutational site in the pericentromeric reg ion of the human X chromosome, justifying the assignment of a new symb ol (MRX26) to our pedigree. Finally, on the basis of the recombination al events observed in the Xq21-q22 region, we have been able to refine the assignment of marker DXS456 to Xq21.33-q22. (C) 1996 Wiley-Liss, Inc.