The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules.
Kallmann syndrome associates hypogonadotropic hypogonadism and 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 III repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration.
Institut Pasteur Unité de Génétique Moléculaire Humaine (CNRS URA 1445), Paris, France.
R
R
Legouis
J P
JP
Hardelin
J
J
Levilliers
J M
JM
Claverie
S
S
Compain
V
V
Wunderle
P
P
Millasseau
D
D
Le Paslier
D
D
Cohen
D
D
Caterina
D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D002461:Cell Line, Transformed; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008894:Milk Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D009710:Nucleotide Mapping; D000857:Olfaction Disorders / Q000235:genetics; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome
C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D008894:Milk Proteins; D009419:Nerve Tissue Proteins; C024471:whey acidic proteins