摘要：目的 用基因连锁分析方法对一个Alport综合征家系的致病基因定位。方法应用聚合酶链反应(PCR)方法分别扩增与2号染色体上Ⅳ型胶原α3和α4链基因(COL4A3／COL4A4)连锁的微卫星遗传标记CA11、PAX3、D2S401及与X染色体上Ⅳ型胶原α5链基因(COL4A5)紧密连锁的微卫星遗传标记2B6、DXS101，找出家系中与疾病连锁的单体型，并计算出Lod score值，从而判定是否存在连锁关系。结果 基因连锁分析提示这个家系致病基因与2号染色体上CA11、PAX3、D2S401一起分离(Lod Score=2．10，9=0)，不与X染色体上2B6及DXS101一起分离(Lod score=0，θ=0．5)。结论 这个Alport综合征家系的致病基因与COL4A3／COL4A4基因连锁。可能因2号染色体上Ⅳ型胶原α3／α4链基因突变致病。

Gene linkage analysis of a Chinese family with Alport syndrome

ZHU Shile ,ZHANG Chengying ,HOU Ping

(Institute of Nephrology,First Hospital,Peking University, Beijing 100034, China)

Abstract：Objective To locate the pathogenetic gene of a Chinese family with Alport syndrome.Methods Genetic linkage analysis was performed using micrositellite markers closely linked with COL4A3/COL4A4 locus on chromosome 2q35-37, and micrositellite markers on chromosome Xq22 flanking the COL4A5 gene locus.The maximum Lod Scores was calculated. Results Genetic linkage analysis revealed co-segregation of the disease with the markers PAX3 ,D2S401 with a maximum Lod Score=2. 10 at zero recombination.Conclusion Mutation in the COL4A3 and COL4A4 gene may cause the autosomal domiant Alport syndrome of this family.

Keywords：Alport syndrome;Collagen type Ⅳ; Gene; Linkage

作者简介：张承英，硕士生，现在武警总医院肾内科

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收稿日期：1999-12-02