Download PDF
J Pediatr Genet 2013; 02(04): 181-189
DOI: 10.3233/PGE-13067
Georg Thieme Verlag KG Stuttgart – New York

ACVRL1 gene variant in a patient with vein of Galen aneurysmal malformation

Ayako Chida
a   Department of Pediatrics, National Defense Medical College, Tokorozawa-city, Saitama, Japan
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
,
Masaki Shintani
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
,
Hajime Wakamatsu
a   Department of Pediatrics, National Defense Medical College, Tokorozawa-city, Saitama, Japan
,
Yoshiyuki Tsutsumi
c   Department of Radiology, National Center for Child Health and Development, Setagaya-ku Tokyo, Japan
,
Yuo Iizuka
d   Department of Radiology, Toho University Ohashi Medical Center, Tokyo, Japan
,
Nanako Kawaguchi
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
,
Yoshiyuki Furutani
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
,
Kei Inai
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
,
Shigeaki Nonoyama
a   Department of Pediatrics, National Defense Medical College, Tokorozawa-city, Saitama, Japan
,
Toshio Nakanishi
b   Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
› Author Affiliations
Subject Editor:
Further Information

Publication History

10 November 2013

03 February 2014

Publication Date:
27 July 2015 (online)

  PDF Download  Permissions and Reprints

Abstract

Although mutations in the RASA1 gene in vein of Galen aneurysmal malformation (VGAM) and an endoglin gene mutation in a VGAM patient with a family history of hereditary hemorrhagic telangiectasia (HHT) have been identified, most VGAM cases have no mutation in these genes. We sought to detect mutations in other genes related to HHT. We screened for mutations in RASA1 and three genes (endoglin, activin receptor-like kinase 1 (ACVRL1), encoding ALK1, and SMAD4) related to HHT in four VGAM patients. One variant (c.652 C>T p.R218W) in ACVRL1 was identified. Immunoblotting revealed that the ALK1-R218W protein could not promote SMAD1/5/8 phosphorylation by BMP9 stimulation. On the other hand, wild-type ALK1 could enhance the phosphorylation as expected. Furthermore, the transcriptional activation of ALK1-R218W was less efficient than that of wild-type ALK1. We identified 1 variant in ACVRL1 in a VGAM patient. These findings suggest that the ACVRL1 variant-R218W may be associated with the pathogenesis of VGAM.

Keywords

ACVRL1 - gene variant - vein of Galen aneurysmal malformation