title: Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
abstract: Recent discoveries have established the existence of a family of skeletal dysplasias caused by dominant mutations in TRPV4. This family comprises, in order of increasing severity, dominant brachyolmia, spondylo-metaphyseal dysplasia Kozlowski type, and metatropic dysplasia. We tested the hypothesis that a further condition, Spondylo-epiphyseal dysplasia (SED), Maroteaux type (MIM 184095; also known as pseudo-Morquio syndrome type 2), could be caused by TRPV4 mutations. We analyzed six individuals with Maroteaux type SED, including three who had previously been reported. All six patients were found to have heterozygous TRPV4 mutations; three patients had unreported mutations, while three patients had mutations previously described in association with metatropic dysplasia. In addition, we tested one individual with a distinct rare disorder, parastremmatic dysplasia (MIM 168400). This patient had a common, recurrent mutation seen in several patients with Kozlowski type spondylo-metaphyseal dysplasia. We conclude that SED Maroteaux type and parastremmatic dysplasia are part of the TRPV4 dysplasia family and that TRPV4 mutations show considerable variability in phenotypic expression resulting in distinct clinical-radiographic phenotypes.
authors.affiliation: Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Lausch
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: André
authors.initials: A
authors.lastname: Megarbané
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitoh
authors.forename: Ok Hwa
authors.initials: OH
authors.lastname: Kim
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.forename: Francesca
authors.initials: F
authors.lastname: Bedeschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedicenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.forename: Margherita
authors.initials: M
authors.lastname: Silengo
authors.forename: Maren
authors.initials: M
authors.lastname: Schmidt-Rimpler
authors.forename: Jurgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zabel
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D016532:Mucopolysaccharidosis II / Q000000981:diagnostic imaging / Q000235:genetics*; D009154:Mutation; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011859:Radiography; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human