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

GPCR: heptahelical transmembrane G-protein-coupled receptor, AD: autosomal dominant.
AR: autosomal recessive.