Multi-organ hereditary hemorrhagic telangiectasia:A case report  

作　　者：Ying-Ling Chen Hong-Yue Jiang Dong-Ping Li Jiang Lin Yun Chen Li-Li Xu Hong Gao 

机构地区：[1]Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [2]Department of Radiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [3]Shanghai Institute of Medical Imaging,Shanghai 200032,China

出　　处：《World Journal of Clinical Cases》2023年第28期6831-6840,共10页世界临床病例杂志

摘　　要：BACKGROUND Type 2 hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant disease and is associated with ALK1 gene mutations.Type 2 HHT patients primarily suffer from recurrent bleeding.There is currently no promising treatment.CASE SUMMARY A 5-year-old Chinese patient(III23)was admitted to Zhongshan Hospital for recurrent melena occurring over 2 mo.She had been experiencing epistaxis for years and had been diagnosed with idiopathic pulmonary hypertension 4 mo before presentation.Abdominal computed tomography examination showed hepatic arteriovenous malformation.Gene testing revealed a c.1121G>A mutation on the ALK1 gene.According to the international diagnostic criteria,this patient was diagnosed with HHT.In addition,8 more family members exhibited HHT symptoms to varying degrees.Gene testing in 5 family members(2 with HHT symptoms and 3 without HHT symptoms)revealed the ALK1 c.1121G>A mutation in the 2 family members with HHT symptoms.This missense mutation results in the substitution of arginine for glutamine at amino acid position 374(R374Q)in the conserved functional kinase domain of ALK1.Biological studies revealed that this mutation decreased the kinase activity of ALK1 and impeded the phosphorylation of its substrate Smad1.Moreover,the R374Q mutant downregulated the protein level of collagen-1,a fibrogenic factor,indicating abnormal fiber generation during vascular formation.CONCLUSION The R374Q mutant of ALK1 and its subsequent influence on fiber generation highly indicated its pathogenic role in this family with type 2 HHT.Detection of this gene mutation will facilitate early diagnosis of suspected type 2 HHT patients,and mechanistic studies will provide insights for future therapy.

关 键 词：Hereditary hemorrhagic telangiectasia PEDIGREE ALK1 Gene mutation Case report 

分 类 号：R596.1[医药卫生—内科学] R544.1[医药卫生—临床医学]