title: Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia.
abstract: Hereditary haemorrhagic teleangiectasia (HHT) is an autosomal dominantly inherited disorder characterised by cutaneous and mucosal telangiectasias, epistaxis and arteriovenous malformations in lung, liver, central nervous system and gastrointestinal tract. Mutations in the genes for endoglin (ENG) and for activin A receptor type II-like kinase 1 (ACVRL1) have been identified to cause HHT. We performed molecular diagnosis in clinically affected probands of 52 HHT families and detected mutations in 34 cases. We report on a total of 19 novel disease-causing mutations, 7 in ENG and 12 in ACVRL1. Three of the novel mutations affected acceptor splice-sites in the ENG gene. RNA analyses in these three patients and in two further patients described before resulted in reduction of the transcript or in a shortened transcript. Furthermore, we identified a family with the mutation c.199C>T in the ACVRL1 gene with liver AVMs. This is the fifth family with this mutation and liver AVMs, clearly indicating a genotype-phenotype correlation for this mutation.
authors.affiliation: Institute of Human Genetics, Georg-August University, 37073 Göttingen, Germany.
authors.forename: Loukas
authors.initials: L
authors.lastname: Argyriou
authors.forename: Stefan
authors.initials: S
authors.lastname: Twelkemeyer
authors.forename: Irakli
authors.initials: I
authors.lastname: Panchulidze
authors.forename: Lars-Erik
authors.initials: LE
authors.lastname: Wehner
authors.forename: Ute
authors.initials: U
authors.lastname: Teske
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Karim
authors.initials: K
authors.lastname: Nayernia
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D000071063:Endoglin; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004247:DNA; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II