Regional localization of a nonspecific X-linked mental retardation gene (MRX59) to Xp21.2-p22.2

Linkage analysis was performed on a four-generation family with nonspecific mental retardation (MRX59). The five affected males, ranging in age from 2 years to 52 years, have a normal facial appearance and mild to severe mental impairment. Four obligate carriers are physically normal and not retarded. A maximum LOD score of 2.41 at straight theta = 0.00 was observed with the microsatellite markers, DMD45 in Xp21.2, DXS989 in Xp22.1, and DXS207 in Xp22.2. Recombinations were detected within the dystrophin gene (DMD) in one of the affected males and between DXS207 and DXS987 in Xp22.2 in one of the carriers. These recombinants define the proximal and distal boundaries of a candidate gene region. Genetic localization of this familial condition made prenatal diagnosis informative for one of the obligate carriers.