H ereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease) is an autosomal dominant genetic disorder characterized by multiple arteriovenous malformations (AVMs). Te common manifestations of this disease are frequent epistaxis, mucocutaneous telangiectasia on typical locations (lips, oral mucosa, and hands), and visceral AVM in the gas- trointestinal tract, liver, lung, and/or central nervous system [1 , 2]. Frequent and recalcitrant bleeding from the nose or mucocutaneous lesions can worsen the patients’ quality of life, and major bleeding from a vis- ceral AVM is sometimes lethal. It is thus very import- ant to diagnose HHT at the earliest possible time point. Four genes (ENG, ACVRL1, SMAD4, and GDF2) have been identifed as pathogenic in HHT [3]. Among these, the mutation of the 2 major genes, ENG and ACVRL1, account for about 80% of all HHT cases [3 , 4]. HHT type 1 (OMIM #187300) is associated with a mutation of ENG with a chromosomal location of 9q34.11. ENG encodes endoglin, which is a component protein of the transforming growth factor beta (TGF-β) receptor complex [5-7]. HHT type 2 (OMIM #600736) is associated with ACVRL1 (ALK1) mutation, which is located in 12q13.13. ACVRL1 encodes a serine/thre- onine-protein kinase receptor R3, i.e., ACVRL1, which is also known as activin A receptor-like kinase 1 (ALK1). ACVRL1 protein acts as a cell-surface receptor for the TGF-β signaling pathway [6 , 7]. Herein, we describe a case of possible HHT in which a novel missense muta- tion of ACVRL1 without mutation in ENG was detected. Acta Med. Okayama, 2020 Vol. 74, No. 2, pp. 165-169 CopyrightⒸ 2020 by Okayama University Medical School. http: // escholarship.lib.okayama- u.ac.jp / amo/ Case Report Identifcation of a Novel ACVRL1 Gene Mutation (c.100T>A, p.Cys34Ser) in a Japanese Patient with Possible Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease) Hiroshi Umemura a § , Katsuhiro Miura b § , Hiromu Naruse a , Yoshihiro Hatta b , Masami Takei b , and Tomohiro Nakayama a ＊ a Division of Laboratory Medicine, Department of Pathology and Microbiology, b Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease) is an autosomal dominant genetic disorder that causes frequent epistaxis, mucocutaneous telangiectasia, and visceral arterio- venous malformations. Four genes (ENG, ACVRL1, SMAD4, and GDF2) have been identifed as pathogenic in HHT. We describe the case of a 50-year-old Japanese man highly suspected of having HHT due to recurrent epistaxis, mucocutaneous telangiectasia, and a family history. Genomic analysis revealed a novel missense mutation of c.100T>A, p.Cys34Ser in the patient’s ACVRL1 gene. We used 6 freeware programs to perform an in silico analysis of this mutation. Te results demonstrated the mutation’s high pathogenicity. Key words: ACVRL1, hereditary hemorrhagic telangiectasia, in silico analysis, missense mutation, Osler-Weber- Rendu disease Received May 30, 2019 ; accepted October 23, 2019. ＊ Corresponding author. Phone : +81-3-3972-8111; Fax : +81-3-5375-8076 E-mail : nakayama.tomohiro@nihon-u.ac.jp (T. Nakayama) § Tese authors contributed equally to this work. Confict of Interest Disclosures: No potential confict of interest relevant to this article was reported.