KISS1R Gene Mutation Analysis In A Chinese Family With IHH

Objective : Idiopathic hypogonadotropic hypogonadism(IHH) is a kind of reproductive endocrine disorder which is closely associated with genetic factors. More than 20 kinds of pathogenic genes have been discovered so far. In this article, we described a Chinese family with IHH to detect the unknown mutation gene and expand the mutation spectrum,which may provide a new approach for the diagnosis and treatment of IHH.Methods:We collected the family members’ clinical information,including chief complaints, physical examinations, laboratory and imaging tests. The genomic DNA was extracted from the peripheral blood.Second-generation sequencing technology was used to determine the proband’s mutation and SIFT software was used to predict the impact of mutation on protein function. Sanger sequencing was used to confirm proband’s mutation results and detect her parents and younger sister.Results:In the inbreeding family, the proband(25-year-old) with type 2 diabetes mellitus(T2DM) showed delayed puberty, primary amenorrhea, infertility, lack of gonadotropins and other typical manifestations of IHH. The proband’s younger brother and sister are alsoshowed delayed puberty. The proband’s parents are first cousins and healthy. Sequencing analysis identified a novel nonsense mutation in exon5 of the KISS1 R gene(c.C983 A,p. S328X). which resulted in a truncated protein with abnormal function. The proband and her sister are in homozygous state and her parents are in heterozygous state. Our results suggested that the inheritance type of mutation is autosomal recessive.Conclusions : We have identified a novel homozygous nonsense mutation in the KISS1 R gene causing IHH which may provide a new approach for the diagnosis and treatment. However, the mechanism of mutation leading to IHH is unclear and whether the mutation is associated with T2 DM is also unknown. These findings warrant further investigation.