CJK 03. Kallmann syndrome in China

Kallmann syndrome (KS) is a genetically heterogeneous disease that combines hypogonadotropic hypogonadism and anosmia/ hyposmia In recently 5 years, we had collected 92 patients and established the follow-up files and disease histories of the patients such as penile length, testicular volume, smell score, hormone levels, karyotype, thyroid function, adrenal cortex, pituitary secretion, glucose and lipid metabolism, GnRH stimulation test and other tests stimulation were recorded. The reproductive hormone therapy were done ranging from 1-5 years in different patients and the level of serum LH, FSH and T as well as the clinical parameters (development of secondary sexual characteristics and sexual function) were significant improvement after reproductive hormone therapy. The sexual function was normal in 3 married patients, and one of them had a child after reproductive hormone therapy. Though the genetic mutation responsible for nearly 30% cases of KS so far, it was scarcely reported in China. We reported a male patient with fertility who had KS as a result of two missense mutations at exon 11 of KAL1 gene, 1690 G>A and 1765 G>A, a G/ A transition in codons 514 and 539, which resulted in the replacement of lysine by glutamic acid, respectively. One of them was a novel mutation. The other two reports were described two intragenic deletions of KAL1 in two KS patients and two of missense mutations (p.C134G and p.C163R) in the KAL1 gene by other authors from China. As it is now believed that most people with KS have an unknown genetic defect, we investigated the genome-wide profile of structural variation and linkage analysis in a consanguineous Han Chinese family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. There was no significant linkage were found in polymorphic markers (LOD values were less than 1.0), but the results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes 1p21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL1, which causes X-linked KS.