A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12

TY - JOUR

T1 - A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12

AU - Johnson, David W.

AU - Berg, Jonathan N.

AU - Gallione, Carol J.

AU - McAllister, Kimberly A.

AU - Warner, Jon P.

AU - Helmbold, Elizabeth A.

AU - Markel, Dorene S.

AU - Jackson, Charles E.

AU - Porteous, Mary E.M.

AU - Marchuk, Douglas A.

N1 - Copyright: © Cold Spring Harbor Laboratory Press.

PY - 1995/8

Y1 - 1995/8

N2 - 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 (θ = 0.04) with D12S339. Mapping of crossovers using haplotype analysis indicated that the candidate region lies in an 11-cm interval between D12S34S 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.

AB - 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 (θ = 0.04) with D12S339. Mapping of crossovers using haplotype analysis indicated that the candidate region lies in an 11-cm interval between D12S34S 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.

KW - Genetics

UR - https://www.scopus.com/pages/publications/0029125615

U2 - 10.1101/gr.5.1.21

DO - 10.1101/gr.5.1.21

M3 - Article

C2 - 8717052

AN - SCOPUS:0029125615

SN - 1054-9803

VL - 5

SP - 21

EP - 28

JO - Genome Research

JF - Genome Research

IS - 1

ER -