Musarella M A
Department of Ophthalmology, Hospital for Sick Children, Toronto, Ont., Canada.
Ophthalmic Paediatr Genet. 1990 Jun;11(2):77-88. doi: 10.3109/13816819009012951.
X-linked retinitis pigmentosa is caused by (a) mutation(s) on the X chromosome. One of the problems encountered in the genetic counselling of this disease is the identification of carrier females who appear ophthalmologically and electrodiagnostically normal. Despite normal testing these women are at risk of transmitting the XLRP gene to their children. Since the biochemical basis of XLRP is unknown, prenatal diagnosis and definitive carrier detection remain elusive. Existing methods of diagnosis and carrier detection are subject to limitations and are dependent on X-inactivation. The application of recombinant DNA probes to families with XLRP has provided a large number of genetic marker loci at the level of DNA. These markers are called restriction fragment length polymorphisms (RFLPs). By analysis of linkage relationships in affected kindreds, the XLRP gene(s) has (have) been localized to two subregions of the short arm of the X chromosome, Xp11 and Xp21. These findings suggest that there may be more than one retinitis pigmentosa gene on the X chromosome. Until further families are studied to clarify the localization(s) of XLRP, neither locus can be excluded if prenatal diagnosis and accurate carrier detection is to be established.
X连锁视网膜色素变性是由X染色体上的一个或多个突变引起的。这种疾病的遗传咨询中遇到的问题之一是识别那些在眼科和电诊断方面表现正常的携带突变基因的女性。尽管检测结果正常,但这些女性仍有将X连锁视网膜色素变性基因传递给其子女的风险。由于X连锁视网膜色素变性的生化基础尚不清楚,产前诊断和明确的携带者检测仍然难以实现。现有的诊断和携带者检测方法存在局限性,并且依赖于X染色体失活。将重组DNA探针应用于患有X连锁视网膜色素变性的家庭,在DNA水平上提供了大量的遗传标记位点。这些标记被称为限制性片段长度多态性(RFLP)。通过分析患病家族中的连锁关系,X连锁视网膜色素变性基因已被定位到X染色体短臂的两个亚区域,即Xp11和Xp21。这些发现表明X染色体上可能存在不止一个视网膜色素变性基因。在进一步研究更多家庭以明确X连锁视网膜色素变性的定位之前,如果要建立产前诊断和准确的携带者检测,这两个位点都不能排除。