An atypical contiguous gene syndrome: molecular studies in a family with X-linked Kallmann's syndrome and X-linked ichthyosis

BACKGROUND AND OBJECTIVE Kallmann's syndrome (KS) is characterized by hypog onadotrophic hypogonadism in association with anosmia or hyposmia, This ent ity can be associated with X-linked ichthyosis (XLI) in a contiguous gene s yndrome, Genetic defects have been demonstrated on the Xp22,3 region explai ning the presence of one or both entities in affected individuals, In this report we describe the molecular findings in four patients, pertaining to a three generation family, with KS which was associated with XLI in two of t hem, MEASUREMENTS Enzymatic activity of steroid sulphatase was measured in leuco cytes, Polymerase chain reaction of the 14 exons of the Kallmann gene (KAL) and of the 5' and 3' extremes of the steroid sulphatase gene was performed in genomic DNA, PCR products of the 14 exons of the KAL gene were purified and sequenced, RESULTS Absence of steroid sulphatase activity and a complete deletion of t he STS gene were demonstrated in both patients with XLI, In all subjects, t he 14 KAL gene exons amplified in a normal fashion; no mutation was documen ted after sequencing all exons, CONCLUSIONS Although it has been proposed recently that the X-linked form o f the disease accounts for the minority of patients with Kallman's syndrome , the pedigree chart of this family demonstrates this inheritance pattern, Various possibilities are mentioned in order to explain the absence of muta tion in the KAL gene, The coexistence, in this family, of Kallman's syndrom e individuals and patients with Kallman's syndrome and X-linked ichthyosis is discussed.