Clinical assessment and genomic landscape of a consanguineous family with three Kallmann syndrome descendants  

作　　者：Shilin Zhang Yanping Tang Tao Wang Jun Yang Ke Rao Lingyun Zhao Wenzhen Zhu Xianghu Meng Shaogang Wang Jihong Liu Weimin Yang Zhangqun Ye 

机构地区：[1]Department of Urology, Tongii Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Department of Genetics, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3]Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

出　　处：《Asian Journal of Andrology》2011年第1期166-171,共6页亚洲男性学杂志（英文版）

摘　　要：Although some genes that cause Kallmann syndrome （KS） have been identified by traditional linkage analysis and candidate gene techniques, the syndrome＇s molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Hart Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants （microdeletions） on chromosomes lp21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL 1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS＇s molecular etiology and generate a list of interesting candidate regions for further studies.Although some genes that cause Kallmann syndrome （KS） have been identified by traditional linkage analysis and candidate gene techniques, the syndrome＇s molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Hart Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants （microdeletions） on chromosomes lp21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL 1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS＇s molecular etiology and generate a list of interesting candidate regions for further studies.

关 键 词：DNA copy number variations HYPOGONADISM Kallmann syndrome male infertility 

分 类 号：Q78[生物学—分子生物学] TP13[自动化与计算机技术—控制理论与控制工程]