| Full text | |
| Author(s): |
Trarbach, Ericka Barbosa
;
Silveira, Leticia Gontijo
;
Latronico, Ana Claudia
[3]
Total Authors: 3
|
| Document type: | Journal article |
| Source: | Pituitary; v. 10, n. 4, p. 381-391, Dec. 2007. |
| Field of knowledge: | Health Sciences - Medicine |
| Abstract | |
The identification of naturally occurring genetic mutations has provided unique insight into the current knowledge of the human hypothalamic-pituitary-gonadal axis. In the past decade, several monogenic causes have been reported in patients with isolated gonadotropin deficiency. Kallmann Syndrome is a clinically and genetically heterogeneous disorder, characterized by isolated hypogonadotropic hypogonadism and anosmia or hyposmia. To date, loss-of-function mutations in the genes encoding anosmin-1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the X-linked and autosomal dominant forms of this syndrome, respectively. More recently, several heterozygous, homozygous or compound heterozygous mutations in the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2) were described in Kallmann syndrome. In addition, complex genetic transmission (digenic inheritance) was recently demonstrated in this condition. Regarding isolated hypogonadotropic hypogonadism without olfactory abnormalities, loss-of-function mutations in the Gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) or the G-protein coupled receptor 54 (GPR54) genes, both encoding transmembrane receptors, have been described, as well as FGFR1 mutations. Finally, mutations of the beta sub-units of LH and FSH have been described in patients with selective gonadotropin deficiency. We review the role of these distinct genetic factors in human isolated hypogonadotropic hypogonadism. (AU) | |
| FAPESP's process: | 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development |
| Grantee: | Ana Claudia Latronico Xavier |
| Support Opportunities: | Research Projects - Thematic Grants |