The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules

Summary Kallmann syndrome associates hypogonadotropic hypogonadismand anosmia and is probably due to a defect in the embryonic migration of olfactory and GnRH-synthesizing neurons. The Kallmann gene had been localized to Xp22.3. In this study 67 kb of genomic DNA, corresponding to a deletion interval containing at least part of the Kallmann gene, were sequenced. Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids. This candidate gene ( ADMLX ) is interrupted in its 3' coding region in the Kallmann patient, in which the proximal end of the KAL deletion interval was previously defined. A 5' end deletion was detected in another Kallmann patient. The predicted protein sequence shows homologies with the fibronectin type 111 repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration.