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.

Saji, N., Kawarai, T., Miyamoto, R., Sato, T., Morino, H., Orlacchio, A., et al. (2015). Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations. JOURNAL OF THE NEUROLOGICAL SCIENCES, 352(1-2), 29-33 [10.1016/j.jns.2015.02.007].

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

ORLACCHIO, ANTONIO;
2015-01-01

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.
2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Aberrant transcript; Arteriovenous malformation; Endoglin; Hereditary hemorrhagic telangiectasia; Intronic mutation; Whole exome sequencing; Adult; Antigens, CD; Arteriovenous Fistula; Asian Continental Ancestry Group; Female; Frameshift Mutation; Humans; Male; Middle Aged; Pulmonary Artery; Pulmonary Veins; Receptors, Cell Surface; Recurrence; Sequence Analysis, DNA; Telangiectasia, Hereditary Hemorrhagic; Exome; Introns; Neurology (clinical); Neurology; Medicine (all)
www.elsevier.com/locate/jns
Saji, N., Kawarai, T., Miyamoto, R., Sato, T., Morino, H., Orlacchio, A., et al. (2015). Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations. JOURNAL OF THE NEUROLOGICAL SCIENCES, 352(1-2), 29-33 [10.1016/j.jns.2015.02.007].
Saji, N; Kawarai, T; Miyamoto, R; Sato, T; Morino, H; Orlacchio, A; Oki, R; Kimura, K; Kaji, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/159282
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