NSMF – Hypogonadotropic Hypogonadism

Mutations in the human nasal embryonic LHRH factor gene NSMF have been identified in 3 of 168 patients (1.8%) with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome (PMID:21300340). One individual harbored compound heterozygous intronic variants (c.629-21G>C and c.629-23C>G) in isolation, while two others carried heterozygous missense alleles alongside mutations in second genes, supporting an oligogenic model (PMID:21300340). In a separate cohort of 65 IHH patients, a novel heterozygous missense change, c.1438A>G (p.Thr480Ala), absent in 100 controls, was detected (PMID:15362570). Functional assays on patient-derived NSMF variants revealed splicing defects and reduced protein expression consistent with haploinsufficiency (PMID:21300340). No segregation beyond probands has been reported. Overall, the evidence meets a ClinGen classification of Limited for the association between NSMF and hypogonadotropic hypogonadism.

References

• Fertility and sterility • 2011 • Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome. PMID:21300340
• Journal of human genetics • 2004 • Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). PMID:15362570

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