A NOVEL AMINOTERMINAL MUTATION IN THE KAL-1 GENE IN A LARGE PEDIGREE WITH X-LINKED KALLMANN-SYNDROME

Kallmann syndrome is characterized by hypogonadotropic hypogonadism an d anosmia. Autosomal dominant, autosomal recessive, and X-Linked patte rns of transmission have been described. The X-linked form of Kallmann syndrome (XLKS) is the least common of the three modes of inheritance and is caused by mutations in the putative cell adhesion protein, KAL -1. In a large pedigree with XLKS, direct sequencing of the KAL-1 gene revealed a duplication of 11 base pairs in exon 1, resulting in a fra meshift and a premature stop at codon 34 of the 680 amino acid protein . The clinical features of the affected individuals in this pedigree p rovide further evidence in support of the idea that XLKS is associated with neurologic features that are not seen in other forms of the synd rome. (C) 1998 Academic Press.