As the mouse nasal embryonic LHRH factor gene (Nelf) encodes a guidance molecule for the migration of the olfactory axon and gonadotropin-releasing hormone neurons, its human homolog, NELF, is a candidate gene for Kallmann syndrome, a disease of idiopathic hypogonadotropic hypogonadism (IHH) with anosmia or hyposmia. We report here characterization of NELF and results of mutation analysis in 65 IHH patients. Assembling EST clones, RACE, and sequencing showed that NELF mapped to 9q34.3 is composed of 16 exons and 15 introns with a 1,590-bp ORF encoding 530 amino acids. RT-PCR on a fetal brain cDNA library revealed five alternatively spliced variants. Among them, NELF-v1 has 93-94% identity at the amino acid level to mouse/rat Nelf, and four other transcripts are also highly conserved among the three species. A 3.0-kb transcript is expressed most highly in the adult and fetal brain, testis, and kidney, indicating that NELF plays a role in the function of these tissues. Mutation screening detected in a patient with IHH one novel heterozygous missense mutation (1438A>G, T480A) at the donor-splice site in exon 15 of NELF. As this mutation was not found in 100 normal control individuals, T480A may be associated with IHH. Four other novel SNPs (102C > T and 1029C > T within the coding region, and two IVS14+47C > T and IVS15+41G > A) were also identified in NELF.

中文翻译：

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人类鼻胚LHRH因子基因NELF的特征以及对65例特发性性腺功能减退性腺功能减退症（IHH）患者的突变筛选。

由于小鼠鼻腔胚胎LHRH因子基因（Nelf）编码嗅觉轴突和促性腺激素释放激素神经元迁移的指导分子，因此其人类同源物NELF是Kallmann综合征的候选基因，Kallmann综合征是一种特发性促性腺激素性性腺功能减退症（ IHH）伴有失眠或低渗。我们在此报告65位IHH患者的NELF表征和突变分析结果。组装EST克隆，RACE和测序表明，映射到9q34.3的NELF由16个外显子和15个内含子组成，具有1,590-bp的ORF，编码530个氨基酸。胎儿脑cDNA文库上的RT-PCR显示了五个选择性剪​​接的变异体。其中，NELF-v1在氨基酸水平上与小鼠/大鼠Nelf具有93-94％的同一性，在这三个物种中，其他四个转录本也高度保守。A 3。0-kb转录本在成年和胎儿脑，睾丸和肾脏中表达最高，表明NELF在这些组织的功能中发挥作用。在患有IHH的患者中，在NELF外显子15的供体剪接位点检测到一个新的杂合错义突变（1438A> G，T480A）。由于在100名正常对照个体中未发现此突变，因此T480A可能与IHH相关。在NELF中还鉴定了其他四个新的SNP（编码区内的102C> T和1029C> T，以及两个IVS14 + 47C> T和IVS15 + 41G> A）。由于在100名正常对照个体中未发现此突变，因此T480A可能与IHH相关。在NELF中还鉴定了其他四个新的SNP（编码区内的102C> T和1029C> T，以及两个IVS14 + 47C> T和IVS15 + 41G> A）。由于在100名正常对照个体中未发现此突变，因此T480A可能与IHH相关。在NELF中还鉴定了其他四个新的SNP（编码区内的102C> T和1029C> T，以及两个IVS14 + 47C> T和IVS15 + 41G> A）。