Kallmann综合征分子遗传学研究进展

Molecular genetics of Kallmann syndrome: An update

Kallmann综合征（KS）是一种临床和遗传异质性疾病，呈家族性或散发性发病。Ks是由胚胎时期嗅球、嗅束的异常发育致使GnRH-1神经细胞不能完成从鼻基板迁移至下丘脑这一过程所引起。GnRH分泌不足导致低促性腺激素性腺功能减退，嗅球、嗅束的异常发育或缺如引起嗅觉丧失。除上述典型症状外，KS患者还可以表现出一些非生殖和非嗅觉表型。KS分子遗传学机制十分复杂，目前只有6个KS致病基因被鉴定。KAL1基因与KS的X连锁隐性遗传模式相关。成纤维细胞生长因子受体1基因（FGFR1／KAL2）和成纤维细胞生长因子8基因（FGFS／KAL6）与常染色体显性遗传模式有关。但是这6个基因的突变只能解释25％～30％的KS病例，提示还有其他KS致病基因有待发现。本文就KS致病基因的研究进展、临床诊断和治疗作一综述。

Kallmann syndrome （KS） is a clinically and genetically heterogeneous disorder that occurs in either an inherited or a sporadic manner. KS results from failed embryonic migration of GnRH-1 neurons from the nasal placode to the hypothalamus, due to the abnormal development of olfactory nerves and bulbs. Hypogonadotropic hypogonadism is related to GnRH deficiency, and anosmia is associated with the absence or hypoplasia of olfactory bulbs 8nd tracts. KS patients can also present some non-reproductive or non-olfactory anomalies in addition to the above typical symptoms. For the high complexity of the molecular genetic mechanism of KS, to date, only 6 KS-related genes have been identified. The KAL1 gene is responsible for the X chromosome-linked recessive form of KS, while the fibroblast growth factor receptor 1 （FGFR1/KAL2） and fibroblast growth factor 8 （FGFS/KAL6） genes are related to the au- tosomal dominant form of the disease. However, the mutations in these 6 genes account for only about 25 - 30% of all KS cases, which suggests that other pathogenic genes involved in KS remain to be discovered. This article presents an overview on the studies of the pathogenic genes, clinical diagnosis and treatment of KS.