一个遗传性出血性毛细血管扩张症家系的临床和遗传学分析

Clinical and Molecular Analysis of Patients from One Chinese Familiy with Heredi tary Hemorrhagic Telangiectasia

目的 :对一个中国遗传性出血性毛细血管扩张症 (HereditaryHemorrhagicTelangiectasia ,HHT)家系的临床表现和遗传缺陷进行分析。方法 :对该HHT家系进行家系调查 ,并对所有成员进行临床检测。用PCR方法扩增ALK 1(Ac tivinReceptor LikeKinase 1)和Endoglin(ENG)基因的所有外显子、外显子 -内含子交界区和 5’、3’非翻译区 ,采用直接测序的方法查找基因突变。结果 :该家系的先证者有反复发作的鼻出血和皮肤粘膜的毛细血管扩张 ,并均有阳性家族史。各器官均未发现动静脉血管畸形。在家系的先证者及其他 4个成员中发现一个位于ALK 1基因第 8外显子G12 32A的错义突变 ,导致Arg 4 11Gln。结论 :HHT的临床表现多样。新错义突变G12 32A(Arg4 11Gln)可能导致HHT2的分子缺陷。该突变为国内首次报道。

Objective:To analysis the clinical features and genetic defects in ALK-1 and Endoglin gene from one Chinese pedigree with hereditary hemorrhag ic telangiectasia (HHT). Method:A detailed medical history and clinical detection was pe rformed on all members of the pedigree and peripheral blood sample collected.A ll exons and intron-exon boundaries of ALK-1 and Endoglin genes were amplified by polymerase chain reaction (PCR) and directly sequenced. Results:All affected members of the pedigree have epistaxis,te langiectases and positive family history of HHT with no systemic arteriovenous m alformations.In the pedigree,G1232A missense mutation in exon 8 of ALK-1 gen e,which changes Arg411 to Gln,is identified in proband and other four clinical ly affected relatives.No mutation of Endoglin gene is detected in all affected individuals.Conclusion:The clinical presentations of HHT are variable.The missense mutation G1232A in exon 8 of ALK-1 gene,first reported in China,is p ossibly the molecular defects casuing the HHT in the pedigree.