常染色体显性视网膜色素变性家系的基因连锁定位和候选基因的序列分析

目的对一常染色体显性视网膜色素变性（RP）家系进行致病基因的连锁定位，并对候选基因进行序列分析。方法在家系中进行全基因组扫描以确定与疾病连锁的染色体区域，对该区域附近的候选基因进行直接序列分析。结果此家系致病基因的最小可能区域（MCR）被定位于19号染色体微卫星标记D19S246和D19S601之间不到5厘摩（cM）的区域。对该区域附近的候选基因进行直接序列分析的结果并未发现致病性基因突变。结论CRX（锥杆细胞同源基因）和PRPF3l基因是该家系的非致病性基因，在19号染色体上可能存在导致常染色体显性视网膜色素变性（adRP）的新的致病基因。

Genetic linkage and mutation analysis of the candidate genes in a big family with autosomal dominant retinitis pigmentosa

ObjectiveTo map the gene responsible for a large Chinese family with autosomal dominant retinitis pigmentosa and sequence the candidate genes.MethodsA large Chinese family with 35 members including 20 retinitis pigmentosa (RP) was identified.Ophthalmologic examinations,including visual acuity,refractive examination,slit-lamp microscope,ophthalmoscope,perimetry and electrophysiologic test were performed on the 20 members with RP.A genome-wide linkage screening was performed in the family using a set of 370 microsatellite markers.Direct sequencing was conducted to the candidate genes.ResultsThe analysis of this RP family met the characters of autosomal dominant heredity.The disease locus was mapped to a minimum critical region(MCR) less than 5cM between D19S246 and D19S601 by linkage analysis.Sequencing of two candidate genes near the MCR showed no mutation.ConclusionThe phenotype of this family is caused by neither CRX gene nor PRPF31 gene.There may be a new gene induced adRP in chromosome 19.