成人型多囊肾病的基因诊断—APKD基因与α珠蛋白基因3’HVR的连锁分析

Gene Diagnosis of Adult Polycystic Kidney Disease --Linkage Analysis Between APKD Gene and α-globin Gene 3'HVR

成人型多囊肾病(adult polycystic kidney disease,APKD)是一种常染色体显性遗传病,临床并不罕见,欧美发病率为1/1000,占慢性肾功能衰竭的9％;我国尚无确切统计.近年来随着B型超声在医学领域中的广泛应用,该病的检出率有所提高.由于APKD症状出现较晚.临床确诊为该病时患者往往已将其致病基因遗传给下一代,因此症状前基因诊断及产前诊断是控制本病的有效措施.1985年Reeders等报道,成人型多囊肾病基因与位于16号染色体短臂上的α珠蛋白基因簇下游(3’端)8 kb处的一高变区(The 3’hypervariable region,3’HVR)具有紧密连锁关系,其重组率为5％;用3’HVR为探针对APKD家系基因组PvuⅡ片段进行RFLP(限制性片段长度多态性)连锁分析,可成功地用于产前诊断.本文首次报道国内5个APKD家系及正常人RFLP分析结果.

Genomic DNA PvuII fragments containing the 3 'HVR from 52 unrelated Chinese of Han nationality varied between 1.7 kb and 10.0 kb and showed high polymorphism. The genomic DNA Pvull fragments from five families with adult polycystic kidney disease (APKD) were analyzed using the α-globin gene 3 ' HVR (hypervariable region) as probe. The results showed a close linkage between 3 'HVR and the APKD gene and segregation according to Mendelian Jaws. The maximum Lod score for linkage between 3 ' HVR and APKD was 3.372 at a recombination fraction θ = 0.01. The a-globin gene 3'HVR probe can therefore be used for presymptomatic gene diagnosis and prenatal diagnosis in the Han ethnic group.