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 language | English |
|---|---|
| Article number | 13635 |
| Pages (from-to) | 29-33 |
| Number of pages | 5 |
| Journal | Journal of the Neurological Sciences |
| Volume | 352 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - May 15 2015 |
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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 journal › Article
}
TY - JOUR
T1 - Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations
AU - Saji, Naoki
AU - Kawarai, Toshitaka
AU - Miyamoto, Ryosuke
AU - Sato, Takahiro
AU - Morino, Hiroyuki
AU - Orlacchio, Antonio
AU - Oki, Ryosuke
AU - Kimura, Kazumi
AU - Kaji, Ryuji
PY - 2015/5/15
Y1 - 2015/5/15
N2 - 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.
AB - 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.
KW - Aberrant transcript
KW - Arteriovenous malformation
KW - Endoglin
KW - Hereditary hemorrhagic telangiectasia
KW - Intronic mutation
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84928366268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928366268&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2015.02.007
DO - 10.1016/j.jns.2015.02.007
M3 - Article
C2 - 25868896
AN - SCOPUS:84928366268
VL - 352
SP - 29
EP - 33
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
M1 - 13635
ER -