GENETIC-ANALYSIS OF A KINDRED WITH X-LINKED MENTAL HANDICAP RETINITIS-PIGMENTOSA

A kindred is described in which X-linked nonspecific mental handicap s egregates together with retinitis pigmentosa. Carrier females are ment ally normal but may show signs of the X-linked retinitis pigmentosa ca rrier state and become symptomatic in their later years. Analysis of p olymorphic DNA markers at nine loci on the short arm of the X chromoso me shows that no crossing-over occurs between the disease and Xp11 mar kers DXS255, TIMP, DXS426, MAOA, and DXS228. The 30% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loc i DXS538 and 5'-dystrophin on the short arm of the X chromosome. The p osterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is 727, suggesting the possibility of a cont iguous-gene-deletion syndrome. No cytogenetic abnormality has been ide ntified.