KALLMANN SYNDROME 1
- OMIM 300836
- Located at chromosome Xp22.3
- Encodes the extracellular matrix protein anosmin 1
- KAL1 comprises 14 exons and the corresponding mRNA (NM_000216.2) encodes a 680 amino acid secreted glycoprotein.
- KAL1 was the first gene to be associated with Kallmann syndrome (KS) (Franco, Guioli et al. 1991; Legouis, Hardelin et al. 1991).
- Mutations in KAL1 account for up to 10–14% of familial KS patients and 8–11% of sporadic KS male patients (Sykiotis, Plummer et al. 2010). Most mutations of KAL1 are nonsense mutations, frameshift mutations or intragenic deletions, all presumably leading to complete gene inactivation.
- Mutations are distributed throughout the gene (Balasubramanian, Dwyer et al. 2010).
- Kallmann syndrome due to KAL1 mutations is inherited in an X chromosome-linked manner) (Franco, Guioli et al. 1991; Legouis, Hardelin et al. 1991). A few oligogenic cases have also been described (Sarfati, Guiochon-Mantel et al. 2010).
- Most mutations of KAL1 are nonsense mutations, frameshift mutations or intragenic deletions, all presumably leading to complete gene inactivation. The 80 different KAL1 point mutations identified to date include only 19 missense mutations. The S396L and R423X mutations of KAL1 have been found together with L173R monoallelic mutations of PROKR2 (Dode, Teixeira et al. 2006; Sarfati, Guiochon-Mantel et al. 2010).
Balasubramanian, R., A. Dwyer, et al. (2010). "Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons." Neuroendocrinology92(2): 81-99.
Dode, C., L. Teixeira, et al. (2006). "Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2." PLoS Genet2(10): e175.
Franco, B., S. Guioli, et al. (1991). "A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules." Nature353(6344): 529-536.
Legouis, R., J. P. Hardelin, et al. (1991). "The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules." Cell67(2): 423-435.
Sarfati, J., A. Guiochon-Mantel, et al. (2010). "A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes." J Clin Endocrinol Metab95(2): 659-669.
Sykiotis, G. P., L. Plummer, et al. (2010). "Oligogenic basis of isolated gonadotropin-releasing hormone deficiency." Proc Natl Acad Sci U S A107(34): 15140-15144.