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
Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Genome Res. 1995 Aug;5(1):21-8. 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.
遗传性出血性毛细血管扩张症（HHT）或奥斯勒-伦杜-韦伯（ORW）病是一种常染色体显性血管发育异常疾病。最初的连锁研究确定了一个位于9q33-q34的ORW基因，但有些家族显然排除了该区域。有人描述了9q3连锁家族与非连锁家族临床表型之间可能存在的相关性，在非连锁家族中观察到肺动静脉畸形的发生率明显较低。在本研究中，我们检查了四个不相关的ORW家族，之前已排除它们与9q33-q34染色体的连锁关系。这四个家族均与12号染色体上的标记建立了连锁关系，与D12S339的联合最大对数计分达到10.77（θ = 0.04）。使用单倍型分析对交叉进行定位表明，候选区域位于12号染色体着丝粒周围区域中D12S345和D12S339之间11厘摩的区间内。因此确定了第二个ORW基因座的图谱位置，该基因座显示肺部受累的发生率显著降低。
