The GnRH receptor plays a central role in regulating gonadotropin synthesis and release, and several mutations in the GNRHR gene have been reported in patients with idiopathic or familial forms of isolated hypogonadotropic hypogonadism (IHH).
A novel missense mutation, Arg(139)His, located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GnRH receptor was identified in the homozygous state in one female with complete HH.
Hypothalamic dysfunction in a female with isolated hypogonadotropic hypogonadism and compound heterozygous TACR3 mutations and clinical manifestation in her heterozygous mother.
The discovery in 1977 of a hypogonadal mouse lacking GnRH (hpg mice) and, in 1986, that the gnrh1 gene was deleted in this mouse, suggested that GNRH1 mutations might also cause human congenital idiopathic (or isolated) hypogonadotropic hypogonadism.This was finally demonstrated in 2009.
Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH).
Our study shows that, in humans, lack of accurate FGFR1 activation can disrupt both brain and hand/foot midline development, and that FGFR1 loss-of-function mutations are responsible for a wider spectrum of clinical anomalies than previously thought, ranging in severity from seemingly isolated hypogonadotropic hypogonadism, through Kallmann syndrome with or without additional features, to Hartsfield syndrome at its most severe end.
FGFR1 mutations cause isolated hypogonadotropic hypogonadism (IHH) with or without olfactory abnormalities, Kallmann syndrome, and normosmic IHH respectively.
Kisspeptin 1 receptor (KISS1R) gene mutations are rare but have recently become an important etiology of normosmic isolated hypogonadotropic hypogonadism (IHH).
Detailed neuroendocrine descriptions were performed in five patients with isolated hypogonadotropic hypogonadism bearing a new GPR54-inactivating mutation.
Homozygous or compound heterozygous loss-of-function mutations in the GPR54 gene have been identified in familial and sporadic patients with isolated hypogonadotropic hypogonadism without olfactory abnormalities.
Inactivating mutations of KISS-1 receptor (KISS1R) have been recently described as a rare cause of isolated hypogonadotropic hypogonadism transmitted as a recessive trait.
Several loss-of-function mutations in GPR54 gene were described to be associated with sporadic and familial normosmic isolated hypogonadotropic hypogonadism phenotype in humans.
It has recently been shown that loss-of-function mutations of the G protein-coupled receptor (GPR)54 lead to isolated hypogonadotropic hypogonadism (IHH) in mice and humans.
Loss of function of the G protein-coupled receptor of kisspeptins (GPR54) was recently described as a new cause of isolated hypogonadotropic hypogonadism.
Loss of function of the G protein-coupled receptor of kisspeptins (GPR54) was recently described as a new cause of isolated hypogonadotropic hypogonadism.