Identification of two novel missense mutations in the KAL1 gene in Han Chinese subjects with Kallmann Syndrome.
OBJECTIVE
To identify mutations in the KAL1, the KAL2, and PROKR2/PROK2 genes and to characterize phenotypic features in 5 Chinese subjects with Kallmann Syndrome (KS) and 6 subjects with normosmic hypogonadotrophic hypogonadism (NHH) in Taiwan.


METHODS
Five unrelated males (age range 22-52 yr) with clinical manifestations of KS and 6 unrelated males (age range 24-47 yr) with NHH were analyzed. In addition, 5 relatives of KS subjects were also evaluated. Genomic DNA extraction, PCR, and DNA sequence analyses were performed using standard procedures.


RESULTS
The 1st patient had a single missense mutation in his copy of the KAL1 gene, a T→G transversion in codon 134 that results in replacement of cysteine by gly cine. The 2nd affected subject had a single missense mutation in the KAL1 gene, a T→C transition in codon 163 that results in replacement of cysteine by arginine. The 3rd case was hemizygous for a nonsense mutation in codon 424 of exon 9 (c.CGA→TGA) of the KAL1 gene. This mutation predicts a markedly truncated protein. Two of the mutations (p.C134G and p.C163R) we identified in the KAL1 gene are novel.


CONCLUSIONS
We identified 3 mutations, including 2 novel mutations, in the KAL1 gene in patients with KS in Taiwan. These data extend the variety of KAL1 gene mutations in KS and further define the role of the KAL1 protein in olfactory bulb development.
Jap
T-S
TS
Section of Biochemistry, Department of Pathology and Laboratory Medicine, Taipei-Veterans General Hospital, Taipei, Taiwan, ROC 112. tsjap@vghtpe.gov.tw
Chiu
C-Y
CY
Lirng
J-F
JF
Won
G-S
GS
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005768:Gastrointestinal Hormones / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D017436:Kallmann Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics; D009830:Olfactory Bulb / Q000000981:diagnostic imaging; D011859:Radiography; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D055815:Young Adult
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D005768:Gastrointestinal Hormones; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C423608:PROK2 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1