PROK2 / PROKR2 signaling and Kallmann syndrome

PROK2 / PROKR2 signaling and Kallmann syndrome

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Kallmann syndrome (KS) is a developmental disease that associates hypogonadism and a deficiency of the sense of smell.The reproductive phenotype of KS results from the primary interruption of the olfactory, vomeronasal and 5 Piece Queen Slat Panel Bedroom terminal nerve fibers in the frontonasal region, which in turn disrupts the embryonic migration of neuroendocrine gonadotropin-releasing hormone (GnRH) synthesizing cells from the nose to the brain.This is a highly heterogeneous genetic disease, and mutations in any of the nine genes identified so far have been found in approximately 30% of the KS patients.

PROKR2 and PROK2, which encode the G protein-coupled prokineticin receptor-2 and its ligand prokineticin-2, respectively, are two of these genes.Homozygous knockout mice for the orthologous genes exhibit a phenotype reminiscent of the KS features, but biallelic mutations in PROKR2 or PROK2 (autosomal recessive mode of disease transmission) have been found only in a minority of the patients, whereas most patients carrying mutations in these genes are heterozygotes.The mutations, mainly missense mutations, have deleterious effects on PROKR2-signaling in transfected cells, ranging Ski de fond - Enfant - Sous-Vetements from defective cell surface-targeting of the receptor to defective coupling to G-proteins or impaired receptor-ligand interaction, but the same mutations have also been found in apparently unaffected individuals, which suggests a digenic/oligogenic mode of inheritance of the disease in heterozygous patients.

This non-Mendelian mode of inheritance has so far been confirmed only in a few patients.However, it may account for the unusually high proportion of KS sporadic cases compared to familial cases.