Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28.

Retinitis pigmentosa (RP) is a group of retinal degeneration characterized by progressive visual field loss, night blindness and pigmentary retinopathy. Its prevalence is in the region of 1-2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life. Although 36-48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance. The X-linked variety ( XLRP ) is found in 14-22% of RP families in the UK. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, with 95% confidence limits of 0-15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.