• PMID: 26031747
• Gene Name: PROKR2
• Condition: Kallmann syndrome, idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)
• Association: The study detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and
• Mutation: KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H
• Population size: 270
• Population details: 270 (70 sporadic Kallmann syndrome cases, 200 Chinese healthy controls)
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Other associated phenotypes: Kallmann syndrome, idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)

Mutation analyses in pedigrees and sporadic cases of ethnic Han Chinese Kallmann syndrome patients

Gu WJ, Zhang Q, Wang YQ, Yang GQ, Hong TP, Zhu DL, Yang JK, Ning G, Jin N, Chen K, Zang L, Wang AP, Du J, Wang XL, Yang LJ, Ba JM, Lv ZH, Dou JT, Mu YM.

Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron-exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients' sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype-phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights. CI - © 2015 by the Society for Experimental Biology and Medicine. FAU - Gu, Wei-Jun AU - Gu WJ AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Zhang, Qian AU - Zhang Q AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Wang, Ying-Qian AU - Wang YQ AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Yang, Guo-Qing AU - Yang GQ AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Hong, Tian-Pei AU - Hong TP AD - Department of Endocrinology, Peking University the Third Hospital, Beijing 100191, China. FAU - Zhu, Da-Long AU - Zhu DL AD - Department of Endocrinology, Drum Tower Hospital, Affiliated to Medical College of Nanjing University, Nanjing 210008, China. FAU - Yang, Jin-Kui AU - Yang JK AD - Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China. FAU - Ning, Guang AU - Ning G AD - Department of Endocrinology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. FAU - Jin, Nan AU - Jin N AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Chen, Kang AU - Chen K AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Zang, Li AU - Zang L AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Wang, An-Ping AU - Wang AP AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Du, Jin AU - Du J AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Wang, Xian-Ling AU - Wang XL AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Yang, Li-Juan AU - Yang LJ AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Ba, Jian-Ming AU - Ba JM AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Lv, Zhao-Hui AU - Lv ZH AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Dou, Jing-Tao AU - Dou JT AD - Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China.