Exploring and expanding the phenotype and genotype diversity in seven Chinese families with spondylo-epi-metaphyseal dysplasia.
Exploring and expanding the phenotype and genotype diversity in seven Chinese families with spondylo-epi-metaphyseal dysplasia.
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探索和扩展七个中国脊椎骨干骺端发育不良家系的表型和基因型多样性
DOI：
10.3389/fgene.2022.960504
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发表时间：
2022
影响因子：
3.7
通讯作者：
Zhang, Zhenlin
中科院分区：
文献类型：
--
作者：
Lv, Shanshan;Zhao, Jiao;Liu, Li;Wang, Chun;Yue, Hua;Zhang, Hao;Li, Shanshan;Zhang, Zhenlin
脊柱-表观-干骺端发育不良(SEMD)是一组具有不同遗传方式的异质性疾病，以不成比例或成比例的矮小为特征。到目前为止，已经发现了30多个致病基因，不同类型的SEMD表现出非常重叠的临床特征，这通常会使诊断复杂化。本研究旨在扩大SEMD在中国人群中的临床和分子谱，并探索其潜在的表型-基因关系。我们招募了7个家系，包括11名受影响的SEMD患者，并仔细分析了他们的临床、放射学和遗传学数据。所有7个先证者都表现出不同程度的矮小，每个先证者都表现出额外的特殊骨骼表现；4个先证者都有骨外表现。7个先证者的X线片显示SEMD的共同特征，包括椎体畸形、骨骺形状不规则和干骺端结构紊乱。在TRPV4(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)基因中发现了7个变异，其中2个是新发现的。两个携带TRPV4变异的家系表现出明显的家庭内和家庭间的异质性。此外，我们还报告了一例由Acan基因突变引起的严重表型的SEMD。本研究拓展了SEMD的表型和遗传谱，为SEMD的表型-基因关系研究提供了证据，为今后SEMD的分子诊断、临床诊断和生殖管理提供了依据。
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.
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影响因子：
20.3
作者：
Kuijpers, TW;Alders, M;Hennekam, RCM
通讯作者：
Hennekam, RCM
影响因子：
5.1
作者：
Ginzberg, H;Shin, J;Durie, PR
通讯作者：
Durie, PR
影响因子：
9.9
作者：
Chen, D. -H.;Sul, Y.;Bird, T.
通讯作者：
Bird, T.
影响因子：
5.2
作者：
Barat-Houari, Mouna;Dumont, Bruno;Touitou, Isabelle
通讯作者：
Touitou, Isabelle
影响因子：
2
作者：
Delague, V;Chouery, E;Mégarbané, A
通讯作者：
Mégarbané, A