Objectives: 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.
Design and patients: 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.