对两个家庭两种罕见遗传性皮肤病(帕-列综合征和Ⅰ型眼皮肤白化病)的共同继承的遗传学研究

作     者：Hewitt C. Hattab F.N. N.S. Thakker 牛新武 

作者机构：Unit of Medical Genetics University of Manchester Manchester M13 OJH United Kingdom 

出 版 物：《世界核心医学期刊文摘（皮肤病学分册）》 (Digest of the World Core Medical JOurnals:Dermatology)

年 卷 期：2005年第1卷第5期

页      面：19-19页

学科分类：1002[医学-临床医学] 100206[医学-皮肤病与性病学] 10[医学] 

主　　题：遗传性皮肤病 眼皮肤白化病 掌跖角化过度 隐性遗传病 酪氨酸酶 染色体带 突变检测 组织蛋白酶 多态现象 序列分析法 

摘      要：The co-occurrence of two rare recessive genetic conditions in apparently unre lated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultan eously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syn drome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both famil ies were tested for polymorphisms at eight microsatellite markers spanning both CTSC and TYR loci. Independent mutations (c.318-1G →A and c.817G →.C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chro mosome bands 11q14.2-14.3, and studies with linked genetic markers suggested th at the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism.