Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13

Fechtner syndrome is an autosomal-dominant variant of Alport syndrome, mani fested by nephritis, sensorineural hearing loss, cataract formation, macrot hrombocytopenia, and polymorphonuclear inclusion bodies. As opposed to auto somal-recessive and X-linked Alport syndromes, which have been genetically well studied, the genetic basis of Fechtner syndrome remains elusive. We ha ve mapped the disease-causing gene to the long arm of chromosome 22 in an e xtended Israeli family with Fechtner syndrome plus impaired liver functions and hypercholesterolemia in some individuals. Six markers from chromosome 22q yielded a LOD score >3.00. A maximum two-point LOD score of 7.02 was ob tained with the marker D22S283 at a recombination fraction of 0. Recombinat ion analysis placed the disease-causing gene in a 5.5-Mb interval between t he markers D22S284 and D22S1167. No collagen genes or genes comprising the basement membrane have been mapped to this region.