title: A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.
abstract: Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber (ORW) disease is an autosomal dominant vascular dysplasia. Initial linkage studies identified an ORW gene localized to 9q33-q34 but with some families clearly excluding this region. A probable correlation in clinical phenotype between the 9q3-linked 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 (theta = 0.04) with D12S339. Mapping of crossovers using haplotype analysis indicated that the candidate region lies in an 11-CM interval between D12S345 and D12S339, 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.
authors.affiliation: Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Johnson
authors.forename: J N
authors.initials: JN
authors.lastname: Berg
authors.forename: C J
authors.initials: CJ
authors.lastname: Gallione
authors.forename: K A
authors.initials: KA
authors.lastname: McAllister
authors.forename: J P
authors.initials: JP
authors.lastname: Warner
authors.forename: E A
authors.initials: EA
authors.lastname: Helmbold
authors.forename: D S
authors.initials: DS
authors.lastname: Markel
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: M E
authors.initials: ME
authors.lastname: Porteous
authors.forename: D A
authors.initials: DA
authors.lastname: Marchuk
mesh_terms: D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D015994:Incidence; D008126:Lod Score; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D010375:Pedigree; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000473:pathology