Vincent P, Plauchu H, Hazan J, Fauré S, Weissenbach J, Godet J
Centre de Génétique Moléculaire et Cellulaire, CNRS-UMR 106, Villeurbanne, France.
Hum Mol Genet. 1995 May;4(5):945-9. doi: 10.1093/hmg/4.5.945.
Hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant vascular disorder which associates epistaxis, mucocutaneous and visceral telangiectases, and recurrent haemorrhage with chronic anaemia and visceral shuntings. Recently, the tumour growth factor (TGF)-beta binding protein endoglin localized to 9q33-34 was identified as responsible for HHT in several large kindreds with pulmonary arteriovenous malformations (PAVMs). Additional linkage studies demonstrated that HHT is a genetically heterogeneous disorder with families unlinked to this region of 9q. In the families in which HHT was not linked to chromosome 9, less PAVMs were present. Furthermore, in one of these families, HHT was found linked to 3p22, where the TGF-beta II receptor is located. In this linkage study, we have analysed DNA from two families, in which HHT was unlinked to chromosome 9q and 3p, and PAVMs were absent, with a series of genetic markers on the centromeric region of chromosome 12. Using two-point linkage analysis, a significant lod score of Zmax = 7.86 at theta = 0.05 was obtained with the D12S85 microsatellite marker.
遗传性出血性毛细血管扩张症（HHT）或朗杜-奥斯勒-韦伯病是一种常染色体显性血管疾病，伴有鼻出血、黏膜皮肤和内脏毛细血管扩张，以及反复出血并伴有慢性贫血和内脏分流。最近，定位于9q33 - 34的肿瘤生长因子（TGF）-β结合蛋白内皮糖蛋白被确定为几个患有肺动静脉畸形（PAVM）的大家族中HHT的致病原因。进一步的连锁研究表明，HHT是一种基因异质性疾病，有些家族与9q的这个区域没有连锁关系。在HHT与9号染色体没有连锁关系的家族中，PAVM的出现较少。此外，在其中一个家族中，发现HHT与位于3p22的TGF-β II受体所在位置连锁。在这项连锁研究中，我们分析了两个家族的DNA，这两个家族中HHT与9号染色体q区和3p区没有连锁关系，且不存在PAVM，我们使用了位于12号染色体着丝粒区域的一系列遗传标记。通过两点连锁分析，在θ = 0.05时，微卫星标记D12S85获得了显著的连锁值Zmax = 7.86。
