title: A novel mutation in ALK-1 causes hereditary hemorrhagic telangiectasia type 2.
abstract: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant bleeding disorder and has two variants, HHT1 and HHT2, associated with mutations in the ENG and ALK-1 genes, respectively. We identified one Chinese HHT2 family to investigate the pathogenic gene and its possible mechanism of action by mutation screening and functional study. One substitution mutation (1717C>T) in exon 10 of the ALK-1 was found by sequencing of all exons of ENG and ALK-1 and caused a R479X mutation in the ALK-1 protein. ALK-1 mRNA and plasma thrombomodulin were measured by real-time quantitative PCR and ELISA, respectively. There was no significant difference in the expression levels of ALK-1 mRNA between patients and healthy individuals. A significantly higher level of thrombomodulin was found in HHT patients. These findings indicate that the mutation causes truncation of the ALK-1 protein at the post-transcriptional level; the plasma thrombomodulin may provide an easy diagnostic indicator in HHT patients.
authors.affiliation: Department of Oral Medicine, Peking University School of Stomatology, 22 South Zhong Guan Cun Street, Beijing 100081, People's Republic of China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Yan
authors.forename: Z P
authors.initials: ZP
authors.lastname: Fan
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: H
authors.initials: H
authors.lastname: Hua
authors.forename: Y Y
authors.initials: YY
authors.lastname: Xu
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000704:Analysis of Variance; D015153:Blotting, Western; D002458:Cell Fractionation; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006472:Oral Hemorrhage / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000097:blood / Q000235:genetics*; D018180:Thrombomodulin / Q000097:blood / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018180:Thrombomodulin; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II