Eye Center of the Second Hospital, Jilin University, Changchun, China.
Department of Pain, the Second Hospital of Jilin University, Changchun, China.
Mol Genet Genomic Med. 2021 Oct;9(10):e1781. doi: 10.1002/mgg3.1781. Epub 2021 Aug 18.
Stickler syndrome is a group of connective tissue disorders that can affect eye (myopia, cataract, and retinal detachment), skeleton (spondyloepiphyseal dysplasia and precocious arthritis), craniofacies (midfacial under development and cleft palate), and inner ear (conductive and sensorineural); with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, and COL9A3 procollagen genes cause Stickler syndrome.
A 16-year-old Mongolian girl approached our clinics with retinal detachment. The proband had vitreous degeneration in both eyes, rhegmatogenous retinal detachment in her right eye, a large area of retina degeneration in her left eye, and coupled with severe myopia. No obvious hearing disorder was found, no abnormalities in bones and joints, and her communication and learning capability were also normal. Further clinical examination showed that the patient's other five family members across three generations had vitreous and retina degenerations. Exome sequencing showed a heterozygous splicing variant in COL2A1 in all patients.
In this case report, a pathogenic splicing variant in the COL2A1 gene was identified in a Mongolian family affected with Stickler syndrome type I by exome sequencing. This heterozygous splicing variant in COL2A1 (NM_001844.4:C.2518-1G>A) that may impair splicing, which was suggested by in silico prediction. Next-generation sequencing is helpful for the differential diagnosis of this clinically variable and genetically heterogeneous disorder.
Stickler 综合征是一组结缔组织疾病，可影响眼睛（近视、白内障和视网膜脱离）、骨骼（脊椎骨骺发育不良和早发性关节炎）、颅面（中面部发育不全和腭裂）和内耳（传导性和感觉神经性）；患者之间的症状严重程度不同。COL2A1、COL11A1、COL11A2、COL9A1、COL9A2 和 COL9A3 前胶原基因的突变导致 Stickler 综合征。
一名 16 岁的蒙古族女孩因视网膜脱离就诊于我院。先证者双眼玻璃体变性，右眼孔源性视网膜脱离，左眼视网膜大面积变性，合并高度近视。无明显听力障碍，无骨骼关节异常，沟通和学习能力正常。进一步临床检查发现，患者的其他五名家族成员三代人都有玻璃体和视网膜变性。外显子组测序显示所有患者的 COL2A1 基因均存在杂合剪接变异。
在本病例报告中，通过外显子组测序，在一个受 Stickler 综合征 I 型影响的蒙古族家庭中发现了 COL2A1 基因的致病剪接变异。该 COL2A1 基因（NM_001844.4：C.2518-1G>A）的杂合剪接变异可能通过计算机预测干扰剪接。下一代测序有助于对这种临床表现多样、遗传异质性的疾病进行鉴别诊断。
