Nature 309, 253 - 255 (17 May 1984); doi:10.1038/309253a0

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

S. S. Bhattacharya^*†, A. F. Wright^*, J. F. Clayton^*, W. H. Price^*†, C. I. Phillips^‡, C. M. E. McKeown^§, M. Jay, A. C. Bird, P. L. Pearson^¶, E. M. Southern^*� & H. J. Evans^*

^*MRC Clinical and Population Cytogenetics Unit and ^†University Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, UK
^‡Department of Ophthalmology, University of Edinburgh, Eye Pavilion, Edinburgh EH3 9HA, UK
^§Department of Clinical Genetics, Birmingham Maternity Hospital, Birmingham B15 2TG, UK
Department of Clinical Ophthalmology, University of London, Institute of Ophthalmology, London WC1H 9QS, UK
^¶Department of Human Genetics, University of Leiden, The Netherlands
^�MRC Mammalian Genome Unit, Department of Zoology, Edinburgh EH9 3JT, UK

Retinitis pigmentosa (RP) is a group of retinal degenerations characterized by progressive visual field loss, night blindness and pigmentary retinopathy¹. 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^2,3. Although 36−48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance^4,5. The X-linked variety (XLRP) is found in 14−22% of RP families in the UK^2,5. 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.

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