Original Investigation

Human Genetics

, Volume 116, Issue 1, pp 8-16

Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients

  • T. G. W. LetteboerAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht Email author 
  • , R. A. ZewaldAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht
  • , E. J. KampingAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht
  • , G. de HaasAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht
  • , J. J. MagerAffiliated withSt. Antonius Hospital
  • , R. J. SnijderAffiliated withSt. Antonius Hospital
  • , D. LindhoutAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht
  • , F. A. M. HennekamAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht
  • , C. J. J. WestermannAffiliated withSt. Antonius Hospital
    • , J. K. Ploos van AmstelAffiliated withDBG-Department of Medical Genetics, University Medical Center Utrecht

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Abstract

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant disorder characterized by an aberrant vascular development. The resulting vascular lesions range from smaller mucocutaneous telangiectases to large visceral arteriovenous malformations, especially in the skin, lung, gastrointestinal tract and the brain. Mutations in the genes encoding endoglin (ENG, chromosome 9q34) and activin A receptor type-like kinase 1 (ALK-1, also named ACVRL1, chromosome 12q13) are associated with HHT1 and HHT2, respectively. We report here on the genetic and molecular heterogeneity found in the HHT population in the Netherlands. Probands of 104 apparently unrelated families were studied and we performed sequence analysis on both the ENG gene and ALK-1 gene. In most of the probands, we found a mutation in one of the two genes: 53% in the ENG gene and 40% in the ALK-1 gene. In 7% of the families no ENG or ALK1 mutation was found. The mutations detected were deletions, insertions, nonsense, missense and splice site mutations. The majority were novel mutations.