Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.
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.
Nishimura
Gen
G
Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Japan.
Dai
Jin
J
Lausch
Ekkehart
E
Unger
Sheila
S
Megarbané
André
A
Kitoh
Hiroshi
H
Kim
Ok Hwa
OH
Cho
Tae-Joon
TJ
Bedeschi
Francesca
F
Benedicenti
Francesco
F
Mendoza-Londono
Roberto
R
Silengo
Margherita
M
Schmidt-Rimpler
Maren
M
Spranger
Jurgen
J
Zabel
Bernhard
B
Ikegawa
Shiro
S
Superti-Furga
Andrea
A
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*
D050916:TRPV Cation Channels; C416986:TRPV4 protein, human