Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia
Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia
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DOI：
10.1136/jmg.2005.035451
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
Westermann, CJJ
中科院分区：
文献类型：
--
作者：
Letteboer, TGW;Mager, JJ;Westermann, CJJ
遗传性出血性毛细血管扩张症（HHT）是一种常染色体显性遗传疾病，其特征为多器官系统血管畸形，导致皮肤粘膜毛细血管扩张和动静脉畸形，主要发生在肺（肺动静脉畸形; PAVM）、脑（脑动静脉畸形; CAVM）和肝（肝动静脉畸形; HAVM）。ENG和ALK-1基因的突变分别导致HHT 1和HHT 2。在这项研究中，进行了基因型-表型分析。一个统一的和良好分类的大组HHT患者及其家庭成员进行了筛选HHT的表现。比较了临床确诊和/或基因确诊（HHT 1或HHT 2）的患者组。确定PAVM、CAVM、HAVM和胃肠道毛细血管扩张症的频率，以建立基因型-表型关系。分析揭示了HHT 1和HHT 2之间以及HHT 1和HHT 2之间在男性和女性之间的差异。PAVM和CAVM在HHT 1中更常见，而HAVM在HHT 2中更常见。此外，在HHT 1中，女性PAVM的患病率高于男性。在HHT 1和HHT 2中，女性中HAVM的频率较高。HHT 1有一个独特的，更严重的表型比HHT 2。男性和女性之间的症状存在差异。有了这些数据，当家庭突变已知时，可以更准确地提供遗传咨询。
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular malformations in multiple organ systems, resulting in mucocutaneous telangiectases and arteriovenous malformations predominantly in the lungs ( pulmonary arteriovenous malformation; PAVM), brain ( cerebral arteriovenous malformation; CAVM), and liver ( hepatic arteriovenous malformation; HAVM). Mutations in the ENG and ALK-1 genes lead to HHT1 and HHT2 respectively. In this study, a genotype-phenotype analysis was performed. A uniform and well classified large group of HHT patients and their family members were screened for HHT manifestations. Groups of patients with a clinically confirmed diagnosis and/ or genetically established diagnosis ( HHT1 or HHT2) were compared. The frequency of PAVM, CAVM, HAVM, and gastrointestinal telangiectases were determined to establish the genotype-phenotype relationship. The analysis revealed differences between HHT1 and HHT2 and within HHT1 and HHT2 between men and women. PAVMs and CAVMs occur more often in HHT1, whereas HAVMs are more frequent in HHT2. Furthermore, there is a higher prevalence of PAVM in women compared with men in HHT1. In HHT1 and HHT2, there is a higher frequency of HAVM in women. HHT1 has a distinct, more severe phenotype than HHT2. There is a difference in the presence of symptoms between men and women. With these data, genetic counselling can be given more accurately when the family mutation is known.