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Abstract：
Spondylo-epi-metaphyseal dysplasia (SEMD) is a heterogeneous group of disorders with different modes of inheritance and is characterized by disproportionate or proportionate short stature. To date, more than 30 disease-causing genes have been identified, and different types of SEMD exhibit greatly overlapping clinical features, which usually complicate the diagnosis. This study was performed to expand the clinical and molecular spectrum of SEMD among Chinese subjects and to explore their potential phenotype-genotype relations. We enrolled seven families including 11 affected patients with SEMD, and their clinical, radiographic, and genetic data were carefully analyzed. All the seven probands showed different degrees of short stature, and each of them exhibited additional specific skeletal manifestations; four probands had extraosseous manifestations. X-rays of the seven probands showed common features of SEMD, including vertebral deformities, irregular shape of the epiphysis, and disorganization of the metaphysis. Seven variants were identified in TRPV4 (c.694C> T, p.Arg232Cys), COL2A1 (c.654 + 1G > C; c.3266_3268del, p.Gly1089del), CCN6 (c.396 T> G, p.Cys132Trp; c.721 T>C, p.Cys241Arg), SBDS (c.258 + 2T> C), and ACAN (c.1508C> A, p.Thr503Lys) genes, and two of them were novel. Two families with TRPV4 variants showed considerable intrafamily and interfamily heterogeneities. In addition, we reported one case of SEMD with a severe phenotype caused by ACAN gene mutation. Our study expands the phenotype and genetic spectrum of SEMD and provides evidence for the phenotype-genotype relations, aiding future molecular and clinical diagnosis as well as procreative management of SEMD.
摘要：
脊椎-表皮-干phy端发育不良（SEMD）是一组具有不同遗传方式的异质性疾病，其特征是不成比例或比例的身材矮小。迄今为止,已经确定了30多个致病基因，不同类型的SEMD表现出极大的重叠临床特征，这通常会使诊断复杂化。本研究旨在扩大中国受试者中SEMD的临床和分子谱，并探讨其潜在的表型-基因型关系。我们招募了七个家庭，包括11名SEMD患者，和他们的临床，射线照相,和遗传数据进行了仔细分析。所有七个先证者都表现出不同程度的身材矮小，每个人都表现出其他特定的骨骼表现；四个先证者有骨外表现。七位先证者的X光显示了SEMD的共同特征,包括脊椎畸形,骨phy的不规则形状，和干phy端混乱。在TRPV4中鉴定出七个变体(c.694C>T，p.Arg232Cys)，COL2A1（c.654+1G>C；c.3266_3268del，p.Gly1089del),CCN6（c.396T>G，p.Cys132Trp;c.721T>C,p.Cys241Arg)，SBDS（c.258+2T>C），和ACAN(c.1508C>A，p.Thr503Lys)基因，其中两个是小说。具有TRPV4变体的两个家族显示出相当大的家族内和家族间异质性。此外,我们报道了1例由ACAN基因突变引起的严重表型的SEMD。我们的研究扩展了SEMD的表型和遗传谱，并为表型-基因型关系提供了证据。有助于SEMD的未来分子和临床诊断以及生殖管理。
