title: Identification of HOXD4 Mutations in Spinal Extradural Arachnoid Cyst.
abstract: Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater and leads to neurological disturbances. We previously showed that familial SEDAC is caused by FOXC2 mutation; however, the causal gene of sporadic SEDAC has not been identified. To identify the causal gene of sporadic SEDAC, we performed whole exome sequencing for 12 subjects with sporadic SEDAC and identified heterozygous HOXD4 loss-of-function mutations in three subjects. HOXD4 haplo-insufficiency causes SEDAC and a transcriptional network containing HOXD4 and FOXC2 is involved in the development of the dura mater and the etiology of SEDAC.
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.|Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ogura
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.|Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Fujibayashi
authors.affiliation: Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Department of Orthopaedic Surgery, Saiseikai Central Hospital, Tokyo, 108-0073, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Okada
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Iwanami
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, 113-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000328:Adult; D016080:Arachnoid Cysts / Q000235:genetics*; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D057895:Haploinsufficiency; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013118:Spinal Cord Diseases / Q000235:genetics*
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C082078:mesenchyme fork head 1 protein