COL2A1和COL11A1患者的基因型-表型相关性。

IF 4.2 1区 医学 Q1 OPHTHALMOLOGY
Antoine Constant , Alejandra Daruich , Federico Bernabei , Matthieu P. Robert , Cyril Burin-Des-Roziers , Sophie Valleix , Dominique Bremond-Gignac , Antoine P. Brézin , Pierre-Raphaël Rothschild
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引用次数: 0

摘要

目的描述和比较COL2A1和COL11A1致病性变异引起的Stickler综合征患者的眼科和眼外特征。设计回顾性横断面研究嵌套在多中心队列研究中。方法回顾性分析2016 - 2024年在巴黎Necker-Enfants Malades医院和Cochin大学医院眼科随访的经分子诊断为Stickler综合征的患者。记录患者的人口统计资料、眼科检查的临床表现和眼外特征。排除了档案不完整、缺乏遗传证据的患者,尽管有相容的临床表型,以及出现罕见变异的患者。结果110例确诊Stickler综合征患者中,COL2A1变异90例(82%),COL11A1变异20例(18%)。末次随访中位年龄为24.4岁[0.9 ~ 77.6],中位随访时间为10.8年[4.2 ~ 27.3]。COL2A1变异体患者视网膜脱离发生率为50% (45/90),COL11A1变异体患者为45%(9/20),组间差异无统计学意义(p= 0.81)。24例(22%)患者发生双侧视网膜脱离,同侧眼视网膜脱离的中位时间为3.0年[0-25.2]年。COL11A1变异患者明显不同于那些COL2A1变异的耳聋频率(50%;10/20比13%,12/90,p = 0.005; CI95% 13.7%; 59.7%]),轴向长度(28.9±3.2毫米和26.3±2.3毫米,p < 0.001; 95%可信区间(+ 1.20,+ 4.02)),视网膜脱离发病年龄(9.8[5.3—-19.7]年和13.3(-66 - 0.5)年,p = 0.006; 95%可信区间[-12.44,-2.19])和平均时间在眼睛的视网膜脱离(2.0[0.2 - 3]年和4.5[0 - 25.2]年,p = 0.009;CI 95%[-7.99 ~ -1.30])。结论:该研究突出了COL2A1-和COL11A1相关的Stickler综合征之间的表型差异,COL11A1变异可能与更严重的眼部表型相关。这种基因型-表型相关性可能有助于改善患者管理和指导预防性干预。这些发现可以支持个性化的随访策略;然而,在更大的队列中进行确认是有必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genotype-Phenotype Correlations of COL2A1 and COL11A1 Patients

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.
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来源期刊
CiteScore
9.20
自引率
7.10%
发文量
406
审稿时长
36 days
期刊介绍: The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented online at www.AJO.com and on ScienceDirect. The American Journal of Ophthalmology publishes Full-Length Articles, Perspectives, Editorials, Correspondences, Books Reports and Announcements. Brief Reports and Case Reports are no longer published. We recommend submitting Brief Reports and Case Reports to our companion publication, the American Journal of Ophthalmology Case Reports. Manuscripts are accepted with the understanding that they have not been and will not be published elsewhere substantially in any format, and that there are no ethical problems with the content or data collection. Authors may be requested to produce the data upon which the manuscript is based and to answer expeditiously any questions about the manuscript or its authors.
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