Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implants, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Clin Lab Anal. 2021 Apr;35(4):e23728. doi: 10.1002/jcla.23728. Epub 2021 Feb 16.
Spondyloepiphyseal dysplasia congenita is an autosomal dominant cartilaginous dysplasia characterized by short trunk, abnormal epiphysis, and flattened vertebral body. Skeletal features of SEDC are present at birth and evolve over time. Other features of SEDC include myopia and/or retinal degeneration with retinal detachment and cleft palate. A mutation in the COL2A1 gene located in 12q13.11 is considered as one of the important causes of SEDC. In 2016, Barat-Houari et al. reported a large number of COL2A1 mutations. Among them, a non-synonymous mutation in COL2A1 exon 37, c.2437G>A (p. Gly813Arg), has been reported to cause SEDC in only one patient from France so far.
We followed up a patient with SEDC phenotype and his family members. The clinical manifestations, physical examination and imaging examination, including X-ray, CT and MRI, were recorded. The whole-exome sequencing was used to detect the patients' genes, and the pathogenic genes were screened out by comparing with many databases.
We report a Chinese patient with SEDC phenotype characterized by short trunk, abnormal epiphysis, flattened vertebral body, narrow intervertebral space, dysplasia of the odontoid process, chicken chest, scoliosis, hip and knee dysplasia, and joint hypertrophy. Gene sequencing analysis showed that the patient had a heterozygous mutation (c.2437G>A; p. Gly813Arg) in the COL2A1 gene. No COL2A1 mutation or SEDC phenotype was observed in his family members. This is the first report of SEDC caused by this mutation in an East Asian family.
This report provides typical clinical, imaging, and genetic evidence for SEDC, confirming that a de novo mutation in the COL2A1 gene, c.2437G>A (p. Gly813Arg), causes SEDC in Chinese population.
先天性脊椎骨骺发育不良是一种常染色体显性遗传性软骨发育不良疾病，其特征为短躯干、异常骨骺和扁平椎体。SED 的骨骼特征在出生时即存在，并随时间演变。SED 的其他特征包括近视和/或视网膜变性伴视网膜脱离和腭裂。位于 12q13.11 的 COL2A1 基因突变被认为是 SEDC 的重要原因之一。2016 年，Barat-Houari 等人报道了大量 COL2A1 基因突变。其中，COL2A1 外显子 37 中的错义突变 c.2437G>A（p.Gly813Arg），迄今为止仅在法国的一位患者中报道与 SEDC 相关。
我们对一位 SEDC 表型患者及其家属进行了随访。记录了患者的临床表现、体格检查和影像学检查，包括 X 线、CT 和 MRI。采用全外显子组测序检测患者的基因，并与多个数据库进行比较筛选致病基因。
我们报告了一位中国 SEDC 表型患者，其特征为短躯干、异常骨骺、扁平椎体、狭窄的椎间隙、齿状突发育不良、鸡胸、脊柱侧凸、髋膝畸形和关节肥大。基因测序分析显示，患者 COL2A1 基因存在杂合突变（c.2437G>A；p.Gly813Arg）。其家族成员未观察到 COL2A1 突变或 SEDC 表型。这是首次在东亚人群中报道由该突变引起的 SEDC。
本报告为 SEDC 提供了典型的临床、影像学和遗传学证据，证实了 COL2A1 基因的新生突变 c.2437G>A（p.Gly813Arg）导致中国人群 SEDC。
