title: Familial Kallmann syndrome: a novel splice acceptor mutation in the KAL gene.
abstract: Kallmann syndrome is an inherited disease which is characterised by anosmia (inability to smell) and hypogonadotropic hypogonadism both of which are thought to occur as a result of a failure of correct neuronal migration. To date the only genetic lesions identified are mutations in the X-linked gene, KAL. We conducted a mutation screen of the KAL gene in a family with Kallmann syndrome. This identified a new mutation in the KAL gene which removed an acceptor site at the junction of exon 6/intron 5. Exon 6 of the KAL gene encodes the C-terminal portion of a fibronectin type III domain may be involved in axonal pathfinding. We presume that the described mutation would result in the removal of exon 6 resulting in a frame shift which terminates the protein prematurely. It has been proposed that both mental illness and vesico-ureteric reflux are associated with mutations in the KAL gene. However, results from the family presented here do not show an association between either trait and the KAL gene mutation.
authors.affiliation: Dept. of Paediatrics & Centre for Hormone Research University of Melbourne, Royal Children's Hospital Parkville, Victoria, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: B
authors.initials: B
authors.lastname: Tridjaja
authors.forename: M J
authors.initials: MJ
authors.lastname: Smith
authors.forename: K M
authors.initials: KM
authors.lastname: Bell
authors.forename: G L
authors.initials: GL
authors.lastname: Warne
authors.forename: A H
authors.initials: AH
authors.lastname: Sinclair
mesh_terms: D002648:Child; D005091:Exons; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics; D014718:Vesico-Ureteral Reflux / Q000235:genetics
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins