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 journalArticle

1 Citation (Scopus)

Abstract

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
Volume352
Issue number1-2
DOIs
Publication statusPublished - May 15 2015

Fingerprint

Exome
Hereditary Hemorrhagic Telangiectasia
Arteriovenous Malformations
Recurrence
Lung
Mutation
Phenotype
Blood Vessels
Early Diagnosis
Cerebrovascular Disorders
Orphaned Children
Genetic Testing
Morphogenesis
Age of Onset
Transforming Growth Factor beta
Amino Acid Sequence
Exons
Proteins
Stroke
Bone and Bones

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations. / Saji, Naoki; Kawarai, Toshitaka; Miyamoto, Ryosuke; Sato, Takahiro; Morino, Hiroyuki; Orlacchio, Antonio; Oki, Ryosuke; Kimura, Kazumi; Kaji, Ryuji.

In: Journal of the Neurological Sciences, Vol. 352, No. 1-2, 13635, 15.05.2015, p. 29-33.

Research output: Contribution to journalArticle

Saji, Naoki ; Kawarai, Toshitaka ; Miyamoto, Ryosuke ; Sato, Takahiro ; Morino, Hiroyuki ; Orlacchio, Antonio ; Oki, Ryosuke ; Kimura, Kazumi ; Kaji, Ryuji. / Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations. In: Journal of the Neurological Sciences. 2015 ; Vol. 352, No. 1-2. pp. 29-33.
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