Review Article
Genetics of Isolated Hypogonadotropic Hypogonadism: Role of GnRH Receptor and Other Genes
Table 1
Genetic causes of Kallmann’s syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (IHH).
| Gene | Gene product | Function | Inheritance | Clinical phenotype | Associated clinical phenotype |
| KAL1 | Anosmin-1 | Cell adhesion | X-linked | KS | Anosmia, bimanual synkinesis, renal agenesis | FGFR1 | Fibroblast-growth-factor receptor 1 | Tyrosine kinase receptor | AD | KS or IHH | Anosmia, cleft lip or palate, ear anomalies, tooth agenesis | FGF8 | Fibroblast growth factor 8 | Ligand of FGFR1 | AD | KS or IHH | NELF | Nasal embryonic LHRH factor | Neuronal migration | AD | KS | Anosmia | CHD7 | Chromodomain- helicase-DNA-binding protein 7 | DNA-binding protein, neural crest development | AD | KS or IHH | CHARGE syndrome: anosmia, coloboma, heart anomaly, choanal atresia, retardation, ear abnormalities | PROKR2 | Prokineticin receptor 2 | GPCR | AD AR | KS or IHH | Anosmia | PROK2 | Prokineticin 2 | Ligand of PROKR2 | AD AR | KS or IHH | Anosmia | WDR11 | WD protein | Interaction with EMX1 | AD | KS or IHH | Anosmia | GPR54/KISS1R | Kisspeptin-1 receptor | GPCR | AR | IHH | None | TACR3 | Neurokinin B receptor | GPCR | AR | IHH | None | TAC3 | Neurokinin B | Ligand of TACR3 | AR | IHH | None | LEPR | leptin receptor | Single transmembrane-domain receptor | AR | IHH | Obesity | LEP | leptin | Fat-regulating hormone | AR | IHH | Obesity | GNRH1 | GnRH | Release of LH and FSH | AR | IHH | None | GNRHR | GnRH receptor | GPCR | AR | IHH | None | LHβ | β-subunit of LH | Ligand of LH/CG receptor | AR | IHH | None | FSHβ | β-subunit of FSH | Ligand of FSH receptor | AR | IHH | None |
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GPCR: heptahelical transmembrane G-protein-coupled receptor, AD: autosomal dominant. AR: autosomal recessive.
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