一种新的FGA基因无义突变导致遗传性无纤维蛋白原血症

目的　对 1例遗传性无纤维蛋白原血症患者及其家系成员进行基因分析,探讨遗传性无纤维蛋白原血症发病的分子机制。方法　凝血酶法与免疫比浊法测定血浆纤维蛋白原 (Fg)含量,提取先证者及其家系成员外周血基因组DNA,PCR法扩增其Fg的FGA、FGB和FGG基因所有外显子和侧翼序列,DNA序列分析Fg的基因异常。将先证者突变序列、家系成员和 50名正常人相应序列的PCR产物用限制性内切酶RsaⅠ消化,以进一步确定基因突变位点并排除基因多态性。结果　用Clauss法检测不到先证者及其父亲的血浆Fg,用免疫比浊法测定时,Fg含量均<0. 02g/L。两人FGA基因外显子 4第 3108位核苷酸发生C→T纯合性改变,使Fg的Aα链第 150位密码子 (CAG,编码Gln)突变为终止密码TAG。先证者及其父亲的FGA基因外显子 4和侧翼序列的PCR产物,不能被RsaⅠ酶切,其母亲及部分家系成员的PCR产物被部分酶切,而正常人和该家系中的 5个成员的PCR产物可被完全酶切。结论　FGA基因(外显子 4)Q150X无义突变导致该家系先证者及其父亲遗传性无Fg血症,家系中部分成员为携带者,此突变是一种国际上尚未报道的新的突变类型。     

遗传性出血性毛细血管扩张症分子机制的研究进展

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性出血性疾病 ,毛细血管扩张和同一部位反复出血是本病的主要临床表现。人们对其分子生物学发病机制尚未完全了解。近年来 ,随着基因定位克隆技术的发展 ,使人们可以在分子水平对其进行研究 ,发现endoglin基因和ALK1基因突变可分别导致该病 ,并发现了多种突变形式 ,这将有利于阐明HHT的发病机制 ,进而为最终治愈该病奠定基础     

遗传性出血性毛细血管扩张症发病机制研究进展及诊治

遗传性出血性毛细血管扩张症（HHT）是一种以出血和血管畸形为特征的常染色体显性遗传病，可分为Ⅰ型和Ⅱ型HHT。目前发现endoglin和Alk-1基因突变可分别导致该病，其中endoglin突变与Ⅰ型HHT密切相关，此外还可能有“二次打击”事件参与毛细血管扩张形成过程，对HHT发病机制的研究也有助于深化血管新生的理解，近年来对该病诊断，治疗进行了新的尝试，一定程度上改变了预后。     

遗传性出血性毛细血管扩张症的研究进展

遗传性出血性毛细血管扩张症是一种常染色体显性遗传病,临床上常表现为鼻衂、毛细血管扩张、内脏(肺、肝和中枢神经系统)损害.其诊断依据临床表现和阳性家族史.本病具有遗传异质性,已知的致病基因为endoglin和ALK1.目前认为遗传性出血性毛细血管扩张症的分子生物学基础是TGF-β信号转导紊乱引起的血管发育异常.本症治疗以对症支持治疗为主.     

遗传性出血性毛细血管扩张症研究进展

遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia,HHT)是以毛细血管结构异常、内皮细胞功能异常为特征的常染色体遗传病.患者可因出血、感染等并发症而死亡.HHT患者主要临床表现为反复鼻衄,皮肤黏膜毛细血管扩张,器官尤其是肝、脑、肺、消化道等内脏血管的动静脉畸形,有明...     

1例肝脏遗传性出血性毛细血管扩张症病人的护理

遗传性出血性毛细血管扩张症（H HT）是一种少见的常染色体显性遗传病,又称奥斯勒韦伯朗迪病,可累及皮肤、肺、胃肠道等全身组织、器官[1]。国外有研究报道,73%的遗传性出血性毛细血管扩张症病人累及肝脏[2]。随着国内报道的日益增多,其护理也逐渐引起重视,现将1例肝脏遗传性出血性毛细血管扩张症（H H HT）病人围术期护理报告如下。     

1例肝脏遗传性出血性毛细血管扩张症病人的护理

<正>遗传性出血性毛细血管扩张症(HHT)是一种少见的常染色体显性遗传病,又称奥斯勒-韦伯-朗迪病,可累及皮肤、肺、胃肠道等全身组织、器官[1]。国外有研究报道,73%的遗传性出血性毛细血管扩张症病人累及肝脏[2]。随着国内报道的日益增多,其护理也逐渐引起重视,现将1例肝脏遗传性出血性毛细血管扩张症(HHHT)病人围术期护理报告如下。1病例介绍2     

遗传性出血性毛细血管扩张症的研究进展

遗传性出血性毛细血管扩张症是一种常染色体显性遗传病，临床上常表现为鼻血衄、毛细血管扩张、内脏(肺、肝和中枢神经系统)损害。其诊断依据临床表现和阳性家族史。本病具有遗传异质性，已知的致病基因为endoglin和ALK1。目前认为遗传性出血性毛细血管扩张症的分子生物学基础是TGF-β信号转导紊乱引起的血管发育异常。本症治疗以对症支持治疗为主。     

遗传性、出血性毛细血管扩张症的超声诊断

目的：观察遗传性、出血性毛细血管扩张症(HHT)，当病变累及肝脏及肝内血管时的诊断。方法：本文报告了6例HHT患者的超声检查。结果：结合复习文献表明该病患者肝血管，特别是肝动脉异常囊状扩张是超声诊断遗传性、出血性毛细血管症的一个新征象。结论：超声诊断HHT可提供一种新的检查方法。     

遗传性出血性毛细血管扩张症2例报道

1　病例介绍患者一 :男性 ,3 2岁。自 7～ 8岁时起经常鼻出血 ,量不多 ,且不频繁。近年来逐渐加重 ,经常出现自发性鼻出血 ,偶发于入睡时 ,且量较多。患者二 :患者一之母 ,55岁 ,亦自幼即有鼻出血 ,且渐加重 ,下肢常有瘀斑。在当地检查出、凝血时间及血小板计数均正常。二人经服用维生素Ｃ治疗 ,均无明显效果 ,遂来我院要求查明出血原因。病史及体检结果见表 1。表 1　出血史及体检患者一患者二齿龈出血史 ( ) ( )鼻出血史 ( ) ( )心、肺、腹部均无异常发现鼻粘膜检查干燥干燥红色隆起的毛细血管手背 ( )直径约 1ｍｍ (- )口唇 ( )直径约 1…     

多个短串联重复序列位点在遗传性出血性毛细血管扩张症基因诊断中的应用

目的建立一种遗传性出血性毛细血管扩张症（HHT）间接连锁分析方法进行基因定位，为进一步查找基因突变位点提供信息。方法采用荧光标记PCR扩增技术、复合PCR技术和基因扫描的方法，对100名无关汉族个体的6个短串联重复序列（short tandem repeat，STR）进行多态性分析，对两个HIIT家系38名成员6个STR位点进行多态性连锁分析和单倍型分析。结果6个STR位点基因型分布均符合Hardy—Weinberg平衡（P〉0．05），杂合度（H）大于0．723，多态信息含量（PIC）大于0．704。两个家系连锁分析结果表明，HHT与12号染色体的ALK-1基因紧密连锁。结论选择的6个STR位点具有较好的多态性，结合基因扫描技术能够应用于HHT的间接连锁分析，该方法快速、准确、客观。     

Hereditary hemorrhagic telangiectasia diagnosed by enteroscopy: a case report

Hereditary hemorrhagic telangiectasia (HHT) is a very rare autosomal dominant multisystemic disease. Patients with this disease usually present with punctate mucocutaneous telangiectasias and arteriovenous malformations. The diagnostic criteria currently in use are the Curaçao criteria. HHT is considered a clinical diagnosis; thus, no imaging or preclinical laboratory is mandatory, and diagnosis and management are performed according to the experience of the treating team. We herein describe a 58-year-old man with no significant medical history who presented with a 15-day history of intermittent hematochezia. He was admitted to the hospital and underwent a series of laboratory tests, including colonoscopy, which showed normal results. Therefore, the patient was discharged with a diagnosis of gastrointestinal bleeding. During his second visit to the emergency room, the doctors requested video capsule endoscopy because of the patient’s history, and a diagnosis of HHT was made. The entire approach and treatment were completed with antegrade double-balloon enteroscopy. This case highlights the importance of endoscopic methods for timely diagnosis and proper management.     

疑似扩张型心肌病的遗传性出血性毛细血管扩张症

目的探讨遗传性出血性毛细血管扩张（hereditary hemorrhagic telangiectasis,HHT）的临床特点,以提高诊断率。方法回顾分析1例疑似扩张型心肌病的HHT临床资料。结果本例因阵发性胸闷、气短5年,加重9d入院。当地医院曾诊断为心力衰竭予利尿剂治疗,症状可暂时缓解。患者有长期自发性鼻出血史及贫血史,皮肤、黏膜有毛细血管扩张表现,结合实验室、心电图、超声及肺动脉血管造影检查结果,确诊为HHT并心功能不全。予相应治疗后病情明显好转出院。结论对临床表现类似扩张型心肌病,且有慢性出血、皮肤黏膜毛细血管扩张及内脏损害者,应警惕HHT可能,及时行相关检查。     

Severe open angle glaucoma in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease. Conjunctival telangiectasias and retinal vascular malformations are known ocular manifestations. We report here the first case of open angle glaucoma in a patient with HHT caused by a nonsense mutation, C471X in the ACVRL1 gene.     

Hereditary hemorrhagic telangiectasia in a sudanese patient: A case report

(HHT) is a rare disorder affecting the skin and body''s internal organs with a tendency for bleeding. We report a case of Sudanese 42‐year‐old with family history of HHT presented with recurrent epistaxis and telangiectasias.     

Hereditary hemorrhagic telangiectasia: demonstration of portosystemic venous shunts using power Doppler sonography and sonographically guided percutaneous transhepatic portovenography.

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease associated with vascular abnormalities, which may occur in any organ. Cases of hereditary hemorrhagic telangiectasia accompanied by intrahepatic portosystemic venous shunts, however, have rarely been described. We report a case of hereditary hemorrhagic telangiectasia in which intrahepatic portosystemic shunts were detected using power Doppler sonography and portovenography with percutaneous transhepatic contrast agent injection. On gray-scale sonography, the common hepatic artery was dilated, and dilated tubular structures mimicking dilated biliary tracts were found. Power Doppler sonography demonstrated the continuity of tortuous vascular channels connecting a branch of the right portal vein to a branch of the right hepatic vein. The dilated vascular channels and tributaries of the right hepatic vein showed a monophasic waveform pattern on spectral analysis. Portovenography showed a tangle of vascular structures connecting with a branch of the right hepatic vein.     

Pancreatic arteriovenous malformation: a rare manifestation of hereditary hemorrhagic telangiectasia

We present Doppler ultrasound, computed tomography and angiography findings of a rare pancreatic arteriovenous malformation associated with hereditary hemorrhagic telangiectasia.     

凝血因子ⅩⅢA基因Arg77Cys错义突变和Arg174stop无义突变致凝血因子ⅩⅢ缺陷的分子机制

本研究以凝血因子ⅩⅢ(FⅩⅢ)基因突变为研究的切入点,从分子水平研究这些突变致病的机制.构建野生型FⅩⅢA重组表达质粒,用定点突变方法获得含有2种突变(Arg77Cys及Arg174stop)的FⅩⅢA重组表达质粒.分别将上述重组质粒通过脂质体介导的基因转移方法转染到COS-7细胞表达;用发色底物法检测转染细胞中FⅩⅢ...     

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK-1 (HHT2) gene now enables a genotype-phenotype correlation. OBJECTIVE: To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers. METHODS: A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest-abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype-phenotype correlations were established. RESULTS: PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1. CONCLUSIONS: Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.