Clinical assessment and genomic landscape of a consanguineous family with three Kallmann syndrome descendants.
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 Han 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 1p21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL1, 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.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Shi-Lin
SL
Zhang
Yan-Ping
YP
Tang
Tao
T
Wang
Jun
J
Yang
Ke
K
Rao
Ling-Yun
LY
Zhao
Wen-Zhen
WZ
Zhu
Xiang-Hu
XH
Meng
Shao-Gang
SG
Wang
Ji-Hong
JH
Liu
Wei-Min
WM
Yang
Zhang-Qun
ZQ
Ye
D000328:Adult; D044466:Asian People / Q000235:genetics; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000857:Olfaction Disorders / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction