A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber disease is an autosomal dominant vascular dysplasia. Initial linkage studies identified an ORW gene localized to ?q33-q34 but with some families clearly excluding this region. A probable correlation in clinical phenotype between the 9q3-1inked families and unlinked families was described with a significantly lower incidence of pulmonary arteriovenous malformations observed in the unlinked families, in this study we examined four unrelated ORW families for which linkage to chromosome 9q33-q34 has been previously excluded. Linkage was established for all four families to markers on chromosome 12, with a combined maximum lod score of 10.77 (0- 0.04) with D12S339. Mapping of crossovers using haplotype analysis indicated that the candidate region lies in an II-cM interval between DI2S345 and D12S337, in the pericentromeric region of chromosome 12. A map location for a second ORW locus is thus established that exhibits a significantly reduced incidence of pulmonary involvement.