Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism

Summary: In this study, researchers aimed to assess the role of mutated Semaphorin 3G (SEMA3G) in causing a syndromic form of HH characterized by intellectual disability and facial dysmorphic features. Through homozygosity mapping and exome sequencing, a novel variant in the SEMA3G gene was identified. Using mouse models, in silico homology modelling, and in vitro cell culture assays, it was found that SEMA3G regulates the migration of GnRH neurons and mutations in SEMA3G affect receptor selectivity which may contribute to HH-related defects.