一个遗传性出血性毛细血管扩张症家系的临床和基因诊断

目的：探讨一个遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia，HHT)家系的临床特征及基因诊断的可行性。方法：收集先证者及家系成员的病史资料并进行临床诊断。同时，对先证者进行致病基因突变检测；鉴定出可能致病性变异后，对家系成员进行特定致病基因突变检测及基因诊断。结果：该家系中4代有5例个体以鼻衄为突出临床表现。先证者临床诊断为HHT；2例在世家系成员为临床疑诊个体。ENG(endoglin)基因5'非编码区c.1-127C>T突变见于先证者和2例临床疑诊个体，未见于其他家系成员；综合临床与基因突变分析2例临床疑诊个体确诊为HHT。结论：HHT临床表现个体差异大，ENG基因c.1-127C>T突变是此HHT家系的可能致病性变异。临床与基因诊断相结合可提高HHT的诊治水平。

Clinical and genetic diagnosis in a hereditary hemorrhagictelangiectasia family

Objective: To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family, and to explore the application of gene mutation testingin HHT diagnosis.Methods: Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria. Sequence analysis ofendoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performedwith PCR and Sanger sequencing technology. Aft er the possible pathogenic mutation was identifi edin the proband, the specifi c mutation was detected in the suspected individuals and part of other family members. Th en the genetic diagnoses were concluded.Results: There were 5 family members in 4 generations manifested with epistaxis. According tothe clinical diagnosis criteria, the proband with epistaxis, mucocutaneous telangiectases, visceralarteriovenous malformation and family history was diagnosed as HHT; while 2 survival familymembers with epistaxis and family history were suspected individuals. A substitution mutationin the 5'-untranslated region(5'-UTR) of ENG c.1-127 C>T was detected in the proband and the2 suspected individuals, which did not exist in other family members. Based on the clinical andgenetic findings, the 2 clinically suspected individuals were diagnosed as HHT.Conclusion: There is great variability of the clinical manifestations among HHT patients. ENG c.1-127 C>T mutation is the possible pathogenic variant of the HHT family. A combination of clinicaland genetic diagnosis could improve the diagnosis and treatment of HHT.