Also, they have demonstrated low or absent levels of expression for EG-VEGF receptors (PROKR1 and PROKR2) in ectopic endometriotic tissues.
EG-VEGF (also known as prokineticin-1) and prokineticin-2 act on 2 receptors, namely, PROKR1 and PROKR2 [14,25,26].
(2) Apart from KAL1 (Xp 22.3), the genes responsible for the KS phenotype are the KAL2 [fibroblast growth factor receptor 1] (FGFR1) gene (10%) and the KAL4 [Prokinetecin receptor 2] (PROKR2) and KAL3 [Prokinetecin 2] (PROK2) (9%) genes.
(2.) Hardelin JP, Dode C, 2008 The complex genetics of Kallmann syndrome: K AL1, FGFR1, FGF8, PROKR2, PROK2, et al.
Lee et al., "Chlamydia trachomatis infection increase fallopian tube PROKR2
via TLR2 and NF-[kappa]B activation resulting in a microenvironment predisposed to ectopic pregnancy," The American Journal of Pathology, vol.
Kallmann syndrome caused by mutations in the PROK2 and PROKR2
genes: pathophysiology and genotype-phenotype correlations.
Increased production of this protein - known as PROKR2
- makes a pregnancy more likely to implant in the Fallopian tube.
Mutations in the prokineticin 2 peptide (PROK2) and its transmembrane domain type 2 receptor (PROKR2
) are newly identified molecular culprits in autosomal KS.
The PROK2 gene encodes prokinetecin 2, an 81 amino acid peptide that signals via the G protein-coupled product of the PROKR2 gene.
Recently, a digenic combination of monoallelic variants in PROKR2 and WDR11 has been reported to be responsible for a pituitary stalk interruption syndrome in a child (46).
Following this guideline, Bergman and colleagues  performed the CHD7 analysis in a cohort of 36 Dutch KS patients (previously excluded to carry mutations in FGFR1, PROK2, PROKR2
, and FGF8), identifying 3 heterozygous CHD7 mutations in patients having same features of CHARGE syndrome.
To date, at least 17 genes have been associated with KS and these include KAL1, FGFR1, PROK2, PROKR2
, FGF8, HS6ST1, CHD7, WDR11, SEMA3A, FGF17, IL17RD, DUSP6, SPRY4, FLRT3, NELF, FEZF1, and CCDC141 (3).