title: Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.
abstract: Hereditary hemorrhagic telangiectasia (HHT), or Osler-Rendu-Weber syndrome, is a heterogeneous inherited disorder characterized by multi-systemic vascular dysplasia and wide variation in its phenotypic expression. Hepatic manifestation is seen in about 8 to 30 % of the patients. The molecular basis for liver involvement is unknown. We screened the two known HHT disease loci, the ALK1 (ACVRL1) and ENG genes, for mutations in a clinically well-characterized group of HHT patients with or without liver involvement. Mutations in the ALK1 gene were detected in eight out of 10 HHT patients with hepatic manifestation. Among nine HHT patients without liver involvement, four had mutations in the ALK1, and three in the ENG genes, respectively. In one patient with hepatic manifestation a mutation was detected in both the ALK1 and ENG genes. No mutation could be detected in two patients with liver involvement and, likewise, in two patients without hepatic manifestation. In this study, we have identified five novel ALK1 and one ENG disease-causing mutations. We conclude that hepatic manifestation in HHT patients is associated with mutations in the ALK1 gene, but rarely with ENG mutations.
authors.affiliation: Institut fuer Humangenetik, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
authors.forename: Heidi K A
authors.initials: HK
authors.lastname: Kuehl
authors.forename: Martin
authors.initials: M
authors.lastname: Caselitz
authors.forename: Sandra
authors.initials: S
authors.lastname: Hasenkamp
authors.forename: Siegfried
authors.initials: S
authors.lastname: Wagner
authors.forename: El-Harith A
authors.initials: el-HA
authors.lastname: El-Harith
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
mesh_terms: D030301:Activin Receptors, Type II; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D000071063:Endoglin; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*; D017384:Sequence Deletion; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D003062:Codon; C064206:ENG protein, human; D000071063:Endoglin; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II