Clinical Phenotype And Molecular Mechanism Of Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemicdisease.The incidence of this disease is1:5000-8000. According to the differentvirulence gene, HHT can be divided into5types: HHT1(ENG gene), HHT2(ACVRL1gene), HHT3and HHT4(the virulence gene have been localized but not yet successfullycloned), juvenile polyposis and HHT syndrome(SMAD4gene). The outpatients fromENT department of PLA General Hospital entered this study. The major performance ofthe proband is repeated heavy spontaneous epistaxis, skin and mucous membranetelangiectasia and visceral arteriovenous malformations. Some patients have a familyhistory. According to the clinical diagnostic criteria reported by Shovlin in2000,9caseswere identified as clinically diagnosed patients,3cases were suspected patients.Selected ENG gene and ACVRL1gene as the candidate genes for screening, designedthe primer for the whole exon, and amplified the target fragment, sequenced the PCRproducts. In this study, a total of7mutation sites were identified in two genes,4of themare novel mutation sites by this study,3had been reported;8patients carried themutation gene,4cases were negative. The protein conservative analysis confirmed thatthe7mutation sites of amino acids were highly conserve, the mutation would lead tochanging of protein structure and the normal function. The result of this study not onlyenriched the HHT gene mutation database, but also provided many information andbasis for the gene screening and genetic counseling of the family member.