Analysis of the KAL1 gene in 19 Japanese patients with Kallmann syndrome

Kallmann syndrome is defined by the association of hypogonadotropic hypogon adism and anosmia. The KAL1 gene is responsible for the X-linked form of Ka llmann syndrome. We analyzed the KAL1 gene in 19 Japanese patients with Kal lmann syndrome, including 3 patients reported previously, using PCR-direct sequencing method. All of 19 patients were sporadic, except for 2 monozygot ic twins. In this study, there were 3 kinds of mutations in the KAL1 gene. One of them was a novel mutation consisting of a G to A substitution in the acceptor site at the junction of intron 6/exon 7. None of the mutations ha ve been reported in countries other than Japan. In male sporadic patients w ith Kallmann syndrome, the incidence of mutations in Japanese patients (14% : 2 of 14 cases) was slightly higher than that in patients in USA (8%). Als o, we found 2 polymorphisms, which were always found together in 6 patients . The severity of hypogonadism was not related to the presence of mutations. Unilateral renal aplasia and mirror movement, which are frequently found in patients with the KAL1 gene mutation, were not related to the sites of mut ations.