title: Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).
abstract: Kallmann syndrome (KAL) combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is due to Gonadotropin Releasing Hormone (GnRH) deficiency and anosmia is related to hypoplasia of the olfactory bulbs. Occasional symptoms include renal agenesis, bimanual synkinesia, cleft lip palate, dental agenesis. KAL is genetically heterogeneous and two genes have so far been identified, namely KAL1 (Xp22.3) and FGFR1/KAL2 (8p12), which underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. We studied a cohort of 98 unrelated Caucasian KAL patients. We identified KAL1 mutations in 14 patients, of which 7 (c.3G>A (p.M1?), g.IVS1+1G>T, c.570_571insA (p.R191fsX14), c.784G>C (p.R262P), c.958G>T (p.E320X), c.1651_1654delinsAGCT (p.P551_E552delinsSX), c.1711T>A (p.W571R)) have not been previously reported. In addition, we found FGFR1 mutations in 7 patients, namely c.303G>A (p.V102I), C.385A>C (p.D129A), c.810G>A (p.V273M), c.1093_1094delAG (p.R365fsX41), c.1561G>A (p.A520T), c.1836_1837insT (p.Y613fsX42), c.2190C>G (p.Y730X), all of which were novel mutations. In this study, unilateral renal agenesis and bimanual synkinesia were exclusively found associated with KAL1mutations, cleft palate and dental agenesia with FGFR1mutations.
authors.affiliation: Laboratoire de biochimie et génétique moléculaire et Institut Cochin, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Albuisson
authors.forename: Chistophe
authors.initials: C
authors.lastname: Pêcheux
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuzina
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wasniewska
authors.forename: Marc
authors.initials: M
authors.lastname: Delpech
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
mesh_terms: D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1