A number of variants of X-linked retinitis pigmentosa (XLRP) have been described. In one variant, listed in the McKusick (McK) catalogue (McKusick 1983) as entry no. 30320, the heterozygotes exhibit a golden metallic or tapetal reflex. Three large pedigrees segregating for XLRP with the characteristic tapetal reflex in the heterozygotes were examined, and the linkage between the XLRP locus and Xp loci, L1.28, OTC, 754, XJ-1.1, pERT87 and C7 was measured. The strongest linkage was found to be between the XLRP locus and OTC. In addition, recombinational evidence drawn from the three pedigrees suggests that the XLRP locus is distal to L1.28 and proximal to 754. This putative location of the XLRP gene between L1.28 and 754 taken together with the tight linkage to OTC, a locus already located between L1.28 and 754, leads us to propose a gene order of centromere-L1.28-OTC/XLRP-754-telomere.
X-linked retinitis pigmentosa (XLRP) is manifested in affected males in their first decade and results in blindness by the third or fourth decade. Carrier detection is difficult since most carrier females show no or only equivocal signs well into or beyond their reproductive years. The genes, or the mutations causing RP have not been identified but at least two have been localised to the short arm of the X chromosome provisionally named RP2 and RP3. Identifying inheritance of one or other of these genes must be done by linkage in families using close, informative DNA markers. Here we report the localisation of a highly informative polymerase chain reaction (PCR) detectable microsatellite marker DXS538 using a previously studied family with X-linked RP3 in which recombination had occurred in the region of importance. The DXS538 dinucleotide repeat locus was previously localised to Xp21 .l-pl1.21 to study RP3 in one XLRP family. Using published RFLP data we narrowed the localisation of DXS538 to the region Xp21 .1-pl1.23. Thus DXS538 is now a convenient diagnostic tool, aiding carrier detection of XLRP in females, as shown in the family presented here.Key words: (CA), dinucleotide repeat microsatellite, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), X-linked retinitis pigmentosa (XLRP).X-linked retinitis pigmentosa (XLRP; also X-linked pigmentary retinal dystrophy) is characterised by progressive contraction of the visual fields, night blindness, widespread pigmentary changes in the retina and an absence of electroretinal responses. Manifestation in affected males begins in the first decade and results in blindness by the third or fourth decade.' Most carrier females show no or only equivocal signs of the defect well into or beyond their reproductive years, making early carrier detection by electrophysiological and psychophysical testsThe localisation of two separate loci for retinitis pigmentosa RP2 and RP3 and a possible third RP6 on the x chromosome makes carrier detection possible by DNA technique^.^.^ Using closely linked restriction fragment length polymorphisms (RFLPs), the segregation of XLRP can be followed for carrier detection. Traditionally this involved Southern blotting using RFLPs which often lacked information because only few variants were possible to distinguish between chromosomes and women were seen as homozygous such that a definite answer is only possible in a few families. In the family studied here the XLRP locus has been previously shown using linkage analysis to be in the distal location (RP3).' However, the RFLPs used in the region of RP3 were not informative since the haplotypes of the family members were almost always identical. Therefore, in the absence of appropriate RFLPs centromeric to the ornithine trans carbamylase (OTC) locus, polymerase chain reaction (PCR) was used to amplify a (CA), repeat microsatellite marker DXS538 to provide information enabling distinction between the normal and disease carrying chromosome. DXS538 (previously lo...
The linkage relationships between the X-linked retinitis pigmentosa (XLRP) locus and seven Xp loci: DXS14, DXS7, OTC, DXS141, DXS148, DXS84 and DXS206 were analysed in one large family in which the heterozygotes exhibited the tapetal reflex. Evidence drawn from two-point and multipoint linkage analysis and a number of triply informative crossovers suggests that the XLRP locus in this family is between DXS7 and DXS84. The putative order of loci on the short arm of the X chromosome is: centromere - DXS14 - DXS7 - OTC - XLRP/DXS141 - DXS148 - DXS84 - DXS206 - telemere.
Summary The early ophthalmoscopic signs of typical retinitis pigmentosa are described, with the support of plain photographs of the fundus oculi. Ten cases, aged between 7 and 14 years, are reported, with others, showing early diagnostic ophthalmoscopic signs. Emphasis is placed on three early signs: retinal vessel narrowing, increased visibility of the choroid and the appearance of white material in the fundus. The association of this white material with pigment clumping is especially pointed out, with the suggestion that it is a secretory product of the pigment epithelium and is situated in or adjacent to the pigment epithelium. Critical ophthalmoscopy, plain fundal photography and leisured study of photographs comparing a suspected case with a normal relative can lead to early diagnosis in many patients in the first two decades of life before “bone‐corpuscle” pigment deposits occur.
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