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.Wetested 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1443-1449 |
| Number of pages | 7 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 152 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2010 |
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Keywords
- Dominant inheritance
- Morquio
- Skeletal dysplasia
- Spondylo-epiphyseal dysplasia
- TRPV4
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. / Nishimura, Gen; Dai, Jin; Lausch, Ekkehart; Unger, Sheila; Megarbané, André; Kitoh, Hiroshi; Kim, Ok Hwa; Cho, Tae Joon; Bedeschi, Francesca; Benedicenti, Francesco; Mendoza-Londono, Roberto; Silengo, Margherita; Schmidt-Rimpler, Maren; Spranger, Jurgen; Zabel, Bernhard; Ikegawa, Shiro; Superti-Furga, Andrea.
In: American Journal of Medical Genetics, Part A, Vol. 152, No. 6, 06.2010, p. 1443-1449.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations
AU - Nishimura, Gen
AU - Dai, Jin
AU - Lausch, Ekkehart
AU - Unger, Sheila
AU - Megarbané, André
AU - Kitoh, Hiroshi
AU - Kim, Ok Hwa
AU - Cho, Tae Joon
AU - Bedeschi, Francesca
AU - Benedicenti, Francesco
AU - Mendoza-Londono, Roberto
AU - Silengo, Margherita
AU - Schmidt-Rimpler, Maren
AU - Spranger, Jurgen
AU - Zabel, Bernhard
AU - Ikegawa, Shiro
AU - Superti-Furga, Andrea
PY - 2010/6
Y1 - 2010/6
N2 - 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.Wetested 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.
AB - 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.Wetested 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.
KW - Dominant inheritance
KW - Morquio
KW - Skeletal dysplasia
KW - Spondylo-epiphyseal dysplasia
KW - TRPV4
UR - http://www.scopus.com/inward/record.url?scp=77952751595&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952751595&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.33414
DO - 10.1002/ajmg.a.33414
M3 - Article
VL - 152
SP - 1443
EP - 1449
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 6
ER -