Elucidation of the pathogenic mechanism for the hypogonadotropic hypogonadism and the development of the standard mutation analyses system in congenital hypogonadotropic hypogonadism.

先天性促性腺功能低下是众所周知的不孕症的代表性疾病，促性腺激素治疗对获得生育能力是有效的。这些疾病的遗传异质性暗示了涉及多个基因的复杂遗传性状（寡原性）的多种致病机制的可能性。建立了WAVE系统的标准突变分析方法，提高了诊断效率。对新发现的突变进行功能分析，揭示了先天性促性腺功能减退症的部分致病机制，涉及各种配体-受体系统。未来，我们计划为突变分析结果和临床数据建立数据库。为了阐明促性腺功能减退症的病理生理学和病因学，下一代测序仪将用于大规模分析。

Congenital hypogonadotropic hypogonadism is a well-known representative disorder of infertility and gonadotropin therapy is effective for gain of fertility. The genetic heterogeneity of these disorders alludes to the possibility of diverse pathogenetic mechanisms underlying a complex genetic trait involving multiple genes(oligogenicity). Establishes a standard mutation analyses method by WAVE system improved the diagnostic efficiency. Also performs functional analysis in newly identified mutations revealed a part of the pathogenic mechanism that involved in various ligand-receptor systems of congenital hypogonadotropic hypogonadism.In the future, we are planning to make database for the results of mutation analyses and clinical data. To elucidated pathophysiology and etiology of hypogonadotropic hypogonadism, next-generation sequencers will be useful for large-scale analysis.