title: FOXC2 mutations in familial and sporadic 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. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC.
authors.affiliation: Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan ; Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Shoji
authors.initials: S
authors.lastname: Yabuki
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogata
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000818:Animals; D016080:Arachnoid Cysts / Q000235:genetics*; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013122:Spinal Diseases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein