Spondylo-Epiphyseal Dysplasia, Maroteaux Type (Pseudo-Morquio Syndrome Type 2), and Parastremmatic Dysplasia are Caused by TRPV4 Mutations
Spondylo-Epiphyseal Dysplasia, Maroteaux Type (Pseudo-Morquio Syndrome Type 2), and Parastremmatic Dysplasia are Caused by TRPV4 Mutations
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DOI：
10.1002/ajmg.a.33414
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发表时间：
2010-06-01
影响因子：
2
通讯作者：
Superti-Furga, Andrea
中科院分区：
文献类型：
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作者：
Nishimura, Gen;Dai, Jin;Superti-Furga, Andrea
最近的发现已经确定了由TRPV 4中的显性突变引起的骨骼发育不良家族的存在。这个家族包括，按照严重程度增加的顺序，显性短肢畸形，脊柱干骺端发育不良Kozlowski型，和metatropic发育不良。我们检验了另一种情况，即Maroteaux型脊柱骨骺发育不良（SED）（MIM 184095;也称为假性Morquio综合征2型）可能由TRPV 4突变引起的假设。我们分析了六个人与Maroteaux型SED，包括三个谁以前曾报告。所有6例患者均发现有杂合子TRPV 4突变; 3例患者有未报告的突变，而3例患者有先前描述的与转移性发育不良相关的突变。此外，我们测试了一个人与一个独特的罕见疾病，parastremmatic发育不良（MIM 168400）。该患者有一个常见的，复发性突变，见于几例Kozlowski型脊柱干骺端发育不良患者。我们的结论是，SED Maroteaux型和parastrematic发育不良是TRPV 4发育不良家族的一部分，TRPV 4突变表现出相当大的变异性表型表达，导致不同的临床放射学表型。(C)2010 Wiley-Liss，Inc.
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. (C) 2010 Wiley-Liss, Inc.