A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12

• Published in: Genome research Vol. 5; no. 1; pp. 21 - 28
• Main Authors: Johnson, D W, Berg, J N, Gallione, C J, McAllister, K A, Warner, J P, Helmbold, E A, Markel, D S, Jackson, C E, Porteous, M E, Marchuk, D A
• Format: Journal Article
• Language: English
• Published: United States 01.08.1995
• Subjects: Chromosome Mapping; Chromosomes, Human, Pair 12 - genetics; Chromosomes, Human, Pair 9 - genetics; Female; Genetic Heterogeneity; Humans; Incidence; Lod Score; Lung - blood supply; Lung - pathology; Male; Pedigree; Telangiectasia, Hereditary Hemorrhagic - genetics; Telangiectasia, Hereditary Hemorrhagic - pathology
• ISSN: 1088-9051
• DOI: 10.1101/gr.5.1.21

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.