COL2A1和COL11A1患者的基因型-表型相关性

Genotype-Phenotype Correlations of COL2A1 and COL11A1 Patients.

作者信息

Constant Antoine, Daruich Alejandra, Bernabei Federico, Robert Matthieu P, Burin-Des-Roziers Cyril, Valleix Sophie, Bremond-Gignac Dominique, Brézin Antoine P, Rothschild Pierre-Raphaël

机构信息

From the Service d'ophtalmologie (Ophtalmopôle) Hôpital Cochin, AP-HP (A.C., F.B., A.P.B., P.R.R.), Paris; Assistance Publique-Hôpitaux de Paris, Université de Paris, Sorbonne Paris Cité (A.C., F.B., A.P.B., P.R.R.), Paris.

Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris Cité University (A.D., M.P.B., D.B.G.), Paris; INSERM, UMRS1138, Team 17, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne Paris Cité University, Centre de Recherche des Cordeliers (A.D., C.B.D.R., S.V., D.B.G., A.P.B.), Paris.

出版信息

Am J Ophthalmol. 2025 Sep 8;281:17-24. doi: 10.1016/j.ajo.2025.09.011.

DOI:10.1016/j.ajo.2025.09.011

PMID:40930209

Abstract

PURPOSE

To describe and compare the ophthalmologic and extraophthalmologic features of patients with Stickler syndrome because of pathogenic variants in COL2A1 and COL11A1.

DESIGN

Retrospective cross-sectional study nested in a multicentric cohort study.

METHODS

Records of patients with a confirmed molecular diagnosis of Stickler syndrome followed up in the ophthalmology department at Necker-Enfants Malades and Cochin University hospitals (Paris) between 2016 and 2024 were retrospectively reviewed. Demographic data, clinical findings from ophthalmologic examination, and extraophthalmologic features were recorded. Patients with an incomplete file, lack of genetic evidence despite a compatible clinical phenotype, and those presenting with rare variants were excluded.

RESULTS

Among 110 patients with confirmed Stickler syndrome, 90 (82%) had a COL2A1 variant and 20 (18%) a COL11A1 variant. The median age at last follow-up was 24.4 years (IQR 0.9-77.6), and the median follow-up duration was 10.8 years (IQR 4.2-27.3). Retinal detachment occurred in 50% of patients with COL2A1 variants (45/90) and 45% of those with COL11A1 variants (9/20), with no statistically significant difference between groups (P = .81). Twenty-four patients (22%) had a bilateral retinal detachment with a median time for a retinal detachment of the fellow eye of 3.0 (IQR 0-25.2) years. The patients with COL11A1 variants were significantly different from those with COL2A1 variants in terms of deafness frequency (50% [10/20] vs 13% [12/90]; P = .005; 95% CI 13.7%, 59.7%), axial lengths (28.9 ± 3.2 mm vs 26.3 ± 2.3 mm; P < .001; 95% CI +1.20, +4.02), age at retinal detachment onset (9.8 [IQR 5.3-19.7] years vs 13.3 [IQR 0.5-66] years; P = .006; 95% CI -12.44, -2.19), and median time to retinal detachment in the fellow eye (2.0 [IQR 0.2-3] years vs 4.5 [IQR 0-25.2] years; P = .009; 95% CI -7.99, -1.30).

CONCLUSIONS

The study highlights phenotypic difference between COL2A1- and COL11A1-related Stickler syndrome, with COL11A1 variants potentially associated with more severe ocular phenotype. Such genotype-phenotype correlations may contribute to refining patient management and guiding prophylactic interventions. These findings could support individualized follow-up strategies; however, confirmation in larger cohorts is warranted.

摘要

目的

描述并比较因COL2A1和COL11A1基因致病性变异导致的斯-利综合征患者的眼科及眼外特征。

设计

嵌套于多中心队列研究中的回顾性横断面研究。

方法

回顾性分析2016年至2024年在巴黎内克尔-儿童医院和科钦大学医院眼科接受随访且确诊为斯-利综合征的患者记录。记录人口统计学数据、眼科检查的临床发现及眼外特征。排除病历不完整、临床表型相符但缺乏基因证据以及存在罕见变异的患者。

结果

在110例确诊为斯-利综合征的患者中，90例（82%）有COL2A1变异，20例（18%）有COL11A1变异。末次随访的中位年龄为24.4岁（四分位间距0.9 - 77.6岁），中位随访时间为10.8年（四分位间距4.2 - 27.3年）。COL2A1变异患者中有50%（45/90）发生视网膜脱离，COL11A1变异患者中有45%（9/20）发生视网膜脱离，两组间差异无统计学意义（P = 0.81）。24例患者（22%）发生双侧视网膜脱离，对侧眼视网膜脱离的中位时间为3.0年（四分位间距0 - 25.2年）。COL11A1变异患者与COL2A1变异患者在耳聋发生率（50% [10/20] 对比13% [12/90]；P = 0.005；95%置信区间13.7%，59.7%）、眼轴长度（28.9 ± 3.2mm对比26.3 ± 2.3mm；P < 0.001；95%置信区间+1.20，+4.02）、视网膜脱离发病年龄（9.8 [四分位间距5.3 - 19.7]岁对比13.3 [四分位间距0.5 - 66]岁；P = 0.006；95%置信区间 - 12.44， - 2.19）以及对侧眼视网膜脱离的中位时间（2.0 [四分位间距0.2 - 3]年对比4.5 [四分位间距0 - 25.2]年；P = 0.009；95%置信区间 - 7.99， - 1.30）方面存在显著差异。