Open access
Novel ACVRL1 variant in a family with hereditary hemorrhagic telangiectasia
Hiroyuki Shimada
Yasuto Sano
Takuma Asahi
T. Iwasa
Y. Kawano
Akiko Ota
J. Machida
S. Hara
H. Muramatsu
H. Morisaki
Yoshihito Tokita
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder mainly caused by pathogenic variants in ACVRL1 or ENG . We identified a novel heterozygous ACVRL1 p.Cys95Ser variant in a Japanese family with HHT. The variant co-segregated with clinical features and was associated with impaired BMP9-induced signaling, as evidenced by reduced cell-surface expression and increased endoplasmic reticulum retention. These findings expand the HHT mutational spectrum and support early genetic diagnosis.