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 hypogonadotrophic hypogonadism in association with anosmia or hyposmia. This entity can be associated with X‐linked ichthyosis (XLI) in a contiguous gene syndrome. Genetic defects have been demonstrated on the Xp22.3 region explaining 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 them. MEASUREMENTS Enzymatic activity of steroid sulphatase was measured in leucocytes. 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 the STS gene were demonstrated in both patients with XLI. In all subjects, the 14 KAL gene exons amplified in a normal fashion; no mutation was documented after sequencing all exons. CONCLUSIONS Although it has been proposed recently that the X‐linked form of 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 mutation in the KAL gene. The coexistence, in this family, of Kallman's syndrome individuals and patients with Kallman's syndrome and X‐linked ichthyosis is discussed.