We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.

中文翻译：

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扩大与 COL2A1 和 COL11A1 基因致病变异相关的表型谱

我们报告了来自 16 个不相关家族的 26 名携带 COL2A1 或 COL11A1 基因变异的个体的临床发现。使用 Sanger 和下一代测序，在 13 个家庭（19 个受影响的个体）中鉴定出 11 个不同的 COL2A1 变异（7 个新变异），所有家庭都被诊断为 1 型 Stickler 综合征（STL）。在 9 个家庭中，出现了 COL2A1 致病变异从头开始 在表型上，我们观察到近视 (95%) 和视网膜脱离 (47%)、关节过度灵活 (92%)、面中部后缩 (84%)、腭裂 (53%) 和不同程度的听力障碍 (50%)。一名患者患有脾动脉瘤。一名携带 COL2A1 致病性变异的受影响个体没有表现出眼部体征，包括没有膜性玻璃体异常的证据。在三个家庭（七个受影响的个体）中，发现了三个新的 COL11A1 变体。具有 de novo 变体的提案显示出极其罕见的 Marshall/STL 重叠。在第二个家族中，唯一常见的临床体征是语后进行性感觉神经性听力障碍（DFNA37）。来自第三个家族的受影响个体具有典型的 STL2 体征。与 COL2A1 或 COL11A1 变异相关的疾病表型谱继续扩大，包括典型的 STL 和各种骨发育不良，但也包括非综合征性听力障碍、孤立性近视伴或不伴视网膜脱离，以及没有临床可检测到的眼部病变的 STL 表型。