The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism.
The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism.
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DOI：
10.1038/nrendo.2009.177
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发表时间：
2009-10
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特发性促性腺功能减退症（IHH）的发病率为每10万新生儿1-10例。大约60%的IHH患者存在相关嗅觉缺失，也称为Kallmann综合征，其特征是完全或部分嗅觉丧失。许多与Kallmann综合征相关的基因突变已被定位为KAL1或FGFR1。然而，这些突变加起来只占卡尔曼综合征病例的15%左右。最近，PROK2和PROKR2的突变与该综合征有关，可能导致另外5-10%的病例。其余40%的IHH患者嗅觉正常。在2003年之前，唯一与正常IHH相关的基因是促性腺激素释放激素受体基因。然而，这种受体的突变被认为只占病例的10%。随后，KISS1R、TAC3和TACR3突变被确定为正常IHH的原因。某些基因，包括PROK2和FGFR1，与嗅觉型和正常型IHH相关。尽管该领域最近取得了进展，但大多数IHH病例的遗传原因仍然未知。这篇综述讨论了与促性腺功能低下疾病相关的基因以及这些基因突变可能导致IHH的分子机制。
Idiopathic hypogonadotropic hypogonadism (IHH) has an incidence of 1–10 cases per 100,000 births. About 60% of patients with IHH present with associated anosmia, also known as Kallmann syndrome, characterized by total or partial loss of olfaction. Many of the gene mutations associated with Kallmann syndrome have been mapped to KAL1 or FGFR1. However, together, these mutations account for only about 15% of Kallmann syndrome cases. More recently, mutations in PROK2 and PROKR2 have been linked to the syndrome and may account for an additional 5–10% of cases. The remaining 40% of patients with IHH have a normal sense of smell. Prior to 2003, the only gene linked to normosmic IHH was the gonadotropin-releasing hormone receptor gene. However, mutations in this receptor are believed to account for only 10% of cases. Subsequently, mutations in KISS1R, TAC3 and TACR3 were identified as causes of normosmic IHH. Certain genes, including PROK2 and FGFR1, are associated with both anosmic and normosmic IHH. Despite recent advances in the field, the genetic causes of the majority of cases of IHH remain unknown. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in IHH.