Argyriou Loukas, Wirbelauer Johannes, Dev Arvind, Panchulidze Irakli, Shoukier Moneef, Teske Ute, Nayernia Karim
Georg-August University Göttingen, Institute of Human Genetics, Göttingen, Germany.
Swiss Med Wkly. 2008 Jul 26;138(29-30):432-6. doi: 10.4414/smw.2008.12135.
Hereditary haemorrhagic telangiectasia (HHT), associated with arteriovenous malformations, is a genetic disease of the vascular system with a frequency of approx. 1:10,000. Genetic diagnosis serves to identify individuals at risk of developing the disease and is a useful tool for genetic counselling purposes.
Here we report on a child presenting severe arteriovenous malformations leading to heart failure. Her mother and grandmother present fewer symptoms of hereditary haemorrhagic telangiectasia. In this study we identify the cause of HHT in the family.
Clinical examination, PCR, DNA sequencing, quantitative PCR, Southern blot, xray, ultrasound, cardiac catheterisation and angiocardiography.
Initially the sequence variant in c.392C>T in the endoglin gene was detected in the grandmother, but not in other affected family members. Further analyses revealed a deletion of exon 1 of endoglin, segregating with the phenotype.
This report points out the need for careful evaluation of molecular genetic findings, particularly in diseases with highly variable phenotype.
遗传性出血性毛细血管扩张症（HHT）与动静脉畸形相关，是一种血管系统的遗传性疾病，发病率约为1:10000。基因诊断有助于识别有患病风险的个体，是遗传咨询的有用工具。
我们在此报告一名患有严重动静脉畸形并导致心力衰竭的儿童。她的母亲和祖母遗传性出血性毛细血管扩张症的症状较少。在本研究中，我们确定了该家族中HHT的病因。
临床检查、聚合酶链反应（PCR）、DNA测序、定量PCR、Southern印迹法、X射线、超声、心导管检查和心血管造影。
最初在祖母中检测到内皮素基因c.392C>T的序列变异，但在其他受影响的家庭成员中未检测到。进一步分析发现内皮素基因外显子1缺失，与表型共分离。
本报告指出需要仔细评估分子遗传学发现，尤其是在表型高度可变的疾病中。
