title: Clinical and genetic characteristics of Chinese patients with hereditary haemorrhagic telangiectasia-associated pulmonary hypertension.
abstract: BACKGROUND
  Mutations in activin receptor-like kinase-1 (ACVRL-1) or endoglin (ENG) are mostly identified in patients with hereditary haemorrhagic telangiectasia (HHT) associated with pulmonary hypertension (PH), but have not yet been studied in Chinese patients.
  
  
  METHODS
  In this study, we investigated the clinical and molecular genetic features of Chinese patients with HHT-associated PH and analysed genotype/phenotype correlations in 14 probands and their relatives. Mutation analyses in ACVRL-1, bone morphogenetic protein receptor type 2 (BMPR2) and ENG were performed in 14 Chinese Han patients with HHT-associated PH.
  
  
  RESULTS
  The overall mutation rate was 71·4%, including 8 ACVRL-1 mutations and 2 ENG mutations, 6 of which were novel. Six patients were identified with arteriovenous malformations (AVMs), including four patients with pulmonary AVMs and two patients with liver AVMs. Five of the patients with AVMs were identified with mutations. Most patients received targeted therapy for PH.
  
  
  CONCLUSIONS
  Our findings have revealed the clinical phenotype and molecular genetic features of HHT-associated PH in Chinese Han patients and indicate that mutations of ACVRL-1 and ENG are genetic predisposing factors in Chinese patients. Our data further addressed clinical management and have provided limited experience in treating this group of disorders.
authors.affiliation: Department of Cardiology, the 4th Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Liu
authors.forename: Mélanie
authors.initials: M
authors.lastname: Eyries
authors.forename: Liang
authors.initials: L
authors.lastname: Wen
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D002648:Child; D000071063:Endoglin; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000959:Antihypertensive Agents; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: ACVRL-1; ENG; gene mutations; hereditary haemorrhagic telangiectasia; pulmonary hypertension