一个疑似X连锁型视网膜色素变性家系的遗传连锁分析的研究

目的对一个疑似X连锁型视网膜色素变性(X-linked retinitis pigmentosa,XLRP)家系进行分析,确定其致病基因的所在位点。方法选取已知XLRP候选基因附近的微卫星位标,用多点参数分析方法计算其最大优势对数值(LOD score),并通过对家系成员单倍型分析,确定该家系致病基因所在的染色体位置。结果位于X染色体长臂的微卫星标记DXS8043与该例遗传家系间最大LOD值小于-2,其他位于X染色体短臂的11个微卫星标记与该例遗传家系LOD值保持在0.5上下,无明显的高值。单倍型结果表明该家系中2例患者兄弟(Ⅲ1、Ⅲ6)和他们的携带者母亲(Ⅱ2)在DXS8051与DXS1214之间拥有在正常成员中不存在的基因型,表明该基因型与疾病共分离,进一步确定了他们X性连锁遗传模式,并且可将致病基因初步定位于DXS8051与DXS1214之间的RP23和RP6基因。结论可以排除该例家系的致病位点与X染色体长臂上的RP24基因的连锁,高度怀疑连锁位点存在于X染色体的短臂的RP23和RP6基因,需另增加位标的信息量,以进一步缩小致病基因所在的具体范围。

Investigation on genetic linkage analysis of a family with X-linked retinitis pigmentosa

Objective To identify the disease locus in a suspect Xlinked retinitis pigmentosa(XLRP) family using genetic linkage analysis.Methods Twelve microsatellite markers were selected from the known gene loci.Haplotype analysis for the familiy was performed to determine the critical region.Linkage analysis was performed using the GENE HUNTER program.Results In this suspect X-linked RP family,the LOD score of the DXS8043 marker was <-2,and the haplotype analysis showed the disease loci segregates with the markers located in RP23 and RP6 region.Conclusion The phenotype of ZSC family was not caused by mutation of RP24 gene,and this family may be linked to RP23 or RP6 loci in the short arm of the X chromosome.