A novel nonsense mutation of the KAL gene in two brothers with Kallmann syndrome

Kallmann syndrome (KS), defined by the association of hypogonadotropic hypo gonadism and anosmia or hyposmia, can be caused by mutations in the KAL gen e on Xp 22.3. This gene encodes an extracellular matrix glycoprotein called anosmin-1, which belongs to the class of cell adhesion molecules. In the a bsence of a functional KAL protein, migration of both olfactory and gonadot ropin-releasing hormone neurons is arrested. A defective anosmin-1 molecule may also play a role in the development of synkinesia and renal agenesis, which are exclusively seen in the X-linked form of KS. We describe the clin ical presentation and molecular diagnosis of the defect in two brothers wit h KS. An X-linked mode of transmission was assumed on the basis of synkines ia and the presence of oligomenorrhoea in the mother. A novel nonsense muta tion was found in exon 13 of the KAL gene, encoding the region of the fourt h fibronectin type III repeat of anosmin-1, which results in an apparently nonfunctional truncated protein. Copyright (C) 2000 S. Karger AG, Basel.