Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).
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.
Albuisson
Juliette
J
Laboratoire de biochimie et génétique moléculaire et Institut Cochin, Paris, France.
Pêcheux
Chistophe
C
Carel
Jean-Claude
JC
Lacombe
Didier
D
Leheup
Bruno
B
Lapuzina
Pablo
P
Bouchard
Philippe
P
Legius
Eric
E
Matthijs
Gert
G
Wasniewska
Malgorzata
M
Delpech
Marc
M
Young
Jacques
J
Hardelin
Jean-Pierre
JP
Dodé
Catherine
C
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*
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1