A novel COL2A1 mutation causing spondyloepiphyseal dysplasia congenita in a Chinese family

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: COL2A1; Chinese population; occipitocervical fusion; odontoid process dysplasia; spondyloepiphyseal dysplasia congenita (SEDC); upper cervical decompression.

FIGURE 1

Pedigree of the Chinese family with spondyloepiphyseal dysplasia congenita. The proband (II‐2) is indicated with the closed symbol

FIGURE 2

Imaging examination findings of the proband (II‐2) at the age of 41. A, Sagittal magnetic resonance imaging (MRI) of the cervical spine. B, Transection MRI of C1. C, MRI revealing high cord signals at C2. MRI (A‐C) show high signal intensity in the cervical spinal cord, dysplasia of the odontoid process, basilar invagination, and upper cervical spinal canal stenosis, which is marked by blue circle. D, Whole spine X‐ray in anteroposterior view. E, Whole spine X‐ray in lateral view. Radiographs show flat vertebral body, narrow intervertebral space, irregular endplates, scoliosis, and hip and knee dysplasia. F, Reconstruction of computed tomography (CT) scan shows upper cervical spinal canal stenosis marked by blue circle. G, Reconstruction of CT angiography showing no obvious vertebral artery stenosis H, Chest CT shows chest compression caused by rib invagination

FIGURE 3

Schematic presentation of the quality control system for identifying candidate variants

FIGURE 4

A, Anteroposterior and lateral cervical spine X‐rays after cervical decompression and occipitocervical fusion. B, Preoperative computed tomography (CT) scan showing upper cervical spinal canal stenosis (red circle). Postoperative CT scan showing the total relief of stenosis (blue circle)