遗传性出血性毛细血管扩张症1例并文献复习

Hereditary hemorrhagic telangiectasia: a case report and literature review

摘要:

目的 探讨遗传性出血性毛细血管扩张症(HHT)的临床特点及诊疗方法，以便对其进行早期诊断，为临床工作提供帮助。方法 回顾性分析1例因“反复鼻出血6年”在广东医科大学附属医院耳鼻咽喉头颈外科就诊患者的临床资料及家系患病情况。应用全外显子组测序技术对先证者进行疑似致病基因筛选，应用Sanger测序对先证者及其父亲进行家系验证。结果 先证者及其父亲均有反复鼻出血、鼻腔黏膜毛细血管扩张表现，先证者弟弟具有脑血管畸形病史。全外显子测序显示先证者携带ENG基因c.1361T>C(p.Leu454Pro)杂合突变，Sanger测序显示其父亲携带相同的变异。结论 ENG基因c.1361T>C(p.Leu454Pro)杂合突变为ENG基因中新突变位点，目前为止，gnomAD数据库、clinvar数据库、ESP数据库、千人数据库、EXAC数据库均未见报道，扩展了HHT致病基因ENG的基因变异谱。

关键词:鼻出血;遗传性出血性毛细血管扩张症;ENG基因;家族史

Abstract:

Objective To explore the clinical features, diagnosis and treatment of hereditary hemorrhagic telangiectasia (HHT)，it will provide help for the early diagnosis of HHT in clinical work. Methods It was retrospectively analyzed for the clinical data and family status of a patient admitted to the Departmant of Otorhinolaryngology Head and Neck Surgery of the Affiliated Hospital of Guangdong Medical University due to “recurrent nasal bleeding for 6 years”. The whole exome sequencing (WES) was used to screen suspected pathogenic genes in probands, and Sanger sequencing was used to verify the pedigree of the probands and their family members. Results Both the proband and his father had recurrent epistaxis and mucous telangiectasia. The younger brother of the proband had a history of cerebrovascular malformation. WES revealed that the proband carried a heterozygous mutation of ENG gene C.1361T>C(p.Leu454Pro), while Sanger sequencing showed that his father carried the same mutation. Conclusion The heterozygous mutation of ENG gene C.1361T>C (p.Leu454Pro) is a novel mutation site in ENG gene, which has not been reported in gnomAD database, clinvar database, ESP database,Thousand Genomes Project database and EXAC database. The novel mutation site of ENG gene extended the gene variation spectrum of HHT pathogenic genes.

Key words:Nasal bleeding;Hereditary hemorrhagic telangiectasia;ENG gene;Family history