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.
Abbreviations:
AD (autosomal dominant), AVM (arteriovenous malformation), CT (computed tomography), ENG (endoglin), ESS (epistaxis severity score), HHT (hereditary hemorrhagic telangiectasia), MRI (magnetic resonance imaging), NGS (next-generation sequencing), PAVM (pulmonary arteriovenous malformation), WES (Whole exome sequencing)Keywords
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Article info
Publication history
Published online: April 01, 2015
Accepted:
February 3,
2015
Received in revised form:
January 16,
2015
Received:
November 2,
2014
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
