Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility.
Here, we review the known normosmic causes of HH, and discuss novel developmental and molecular mechanisms underlying KS; finally, we introduce three novel genes (NELF, PKR2, and CHD7) that may be associated with some phenotypic features of KS.
The phenotype of the Pkr2(-/-) mice showed similarity to the clinical features of Kallmann syndrome, a human disease characterized by association of hypogonadotropic hypogonadism and anosmia.