title: X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene.
abstract: Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. This syndrome is from a defect in the embryonic migratory pathway of gonadotropin-releasing hormone synthesizing neurons and olfactory axons. A candidate gene for the X chromosome-linked form of the syndrome was recently isolated by using a positional cloning strategy based on deletion mapping in the Xp22.3 region. With the PCR, two exons of this candidate gene were amplified on the genomic DNAs from 18 unrelated patients affected with the X chromosome-linked Kallmann syndrome. Three different base transitions--all leading to a stop codon--and one single-base deletion responsible for a frameshift were identified. We thus conclude that the candidate gene is the actual KAL gene responsible for the X chromosome-linked Kallmann syndrome. Furthermore, unilateral renal aplasia in two unrelated patients carrying a stop mutation indicates that the KAL gene is itself responsible for this Kallmann syndrome-associated anomaly. The gene is, therefore, also involved in kidney organogenesis. Additional neurologic symptoms in Kallmann patients are also discussed.
authors.affiliation: Unité de Génétique Moléculaire Humaine, Institut Pasteur, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Hardelin
authors.forename: J
authors.initials: J
authors.lastname: Levilliers
authors.forename: I
authors.initials: I
authors.lastname: del Castillo
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Salmon
authors.forename: R
authors.initials: R
authors.lastname: Legouis
authors.forename: S
authors.initials: S
authors.lastname: Blanchard
authors.forename: S
authors.initials: S
authors.lastname: Compain
authors.forename: P
authors.initials: P
authors.lastname: Bouloux
authors.forename: J
authors.initials: J
authors.lastname: Kirk
authors.forename: C
authors.initials: C
authors.lastname: Moraine
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D007006:Hypogonadism / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000857:Olfaction Disorders / Q000235:genetics*; D010375:Pedigree; D014176:Protein Biosynthesis; D013577:Syndrome; D014960:X Chromosome