Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations

Naoki Saji, Toshitaka Kawarai, Ryosuke Miyamoto, Takahiro Sato, Hiroyuki Morino, Antonio Orlacchio, Ryosuke Oki, Kazumi Kimura, Ryuji Kaji

Research output: Contribution to journalArticlepeer-review


Abstract Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in patients with cerebrovascular disease. Pulmonary arteriovenous malformation (PAVM) is one of the complications in HHT and occasionally is causative for life-threatening embolic stroke. Several genetic defects have been reported in patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype variations, including age-at-onset of vascular events, often make an early diagnosis difficult. We present here a Japanese family with a novel intronic heterozygous mutation of ENG, which was identified using whole exome sequencing (WES). The intronic mutation, IVS3 + 4delAGTG, results in in-frame deletion of exon 3 and would produce a shorter ENG protein lacking the extracellular forty-seven amino acid sequences, which is located within the orphan domain. Our findings highlight the importance of the domain for the downstream signaling pathway of transforming growth factor-beta and bone morphogenesis protein superfamily receptors. Considering the phenotype variations and the available treatment for vascular complications, an early diagnosis using genetic testing, including WES, should be considered for individuals at risk of HHT.

Original languageEnglish
Article number13635
Pages (from-to)29-33
Number of pages5
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - May 15 2015


  • Aberrant transcript
  • Arteriovenous malformation
  • Endoglin
  • Hereditary hemorrhagic telangiectasia
  • Intronic mutation
  • Whole exome sequencing

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)


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