A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1.
Fibroblast growth factor receptor 1 (FGFR1) is one of the causative genes for Kallmann syndrome (KS), which is characterized by isolated hypogonadotropic hypogonadism with anosmia/hyposmia. The third immunoglobulin-like domain (D3) of FGFR1 has the isoforms FGFR1-IIIb and FGFR1-IIIc, which are generated by alternative splicing of exons 8A and 8B, respectively. To date, the only mutations to have been identified in D3 of FGFR1 are in exon 8B. We performed mutation analysis of FGFR1 in a 23-year-old female patient with KS and found a missense mutation (c.1072C>T) in exon 8A of FGFR1. The c.1072C>T mutation was not detected in her family members or in 220 normal Japanese and 100 Caucasian female controls. No mutation in other KS genes, KS 1, prokineticin-2, prokineticin receptor-2 and FGF-8 was detected in the affected patient or in her family members. Therefore, this is the first case of KS carrying a de novo missense mutation in FGFR1 exon 8A, suggesting that isoform FGFR1-IIIb, as well as isoform FGFR1-IIIc, plays a crucial role in the pathogenesis of KS.
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan. kiyonori@nagasaki-u.ac.jp
Kiyonori
K
Miura
Shoko
S
Miura
Koh-Ichiro
K
Yoshiura
Stephanie
S
Seminara
Daisuke
D
Hamaguchi
Norio
N
Niikawa
Hideaki
H
Masuzaki
D017398:Alternative Splicing; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
D017931:DNA Primers; D020033:Protein Isoforms; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1