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 

作者机构：Department of Urology Tongii Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Genetics School of Basic Medical Sciences Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Radiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2011年第13卷第1期

页      面：166-171页

核心收录：

学科分类：07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 090102[农学-作物遗传育种] 071102[理学-系统分析与集成] 0710[理学-生物学] 0711[理学-系统科学] 0901[农学-作物学] 0836[工学-生物工程] 081101[工学-控制理论与控制工程] 0811[工学-控制科学与工程] 081103[工学-系统工程] 

主　　题：DNA copy number variations hypogonadism Kallmann syndrome male infertility 

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.