Abstract：
OBJECTIVE: To describe four Finnish families with epithelial recurrent erosion dystrophy (ERED) caused by the pathogenic variant c.3156C>T in collagen type XVII alpha 1 chain gene (COL17A1).
METHODS: Eleven affected and two unaffected individuals underwent clinical ophthalmological examination, anterior segment photography, and corneal topography. Two of them underwent phototherapeutic keratectomy (PTK). Genetic analysis included both next-generation and Sanger sequencing. Specimens from the manual keratectomy of one patient were available for ophthalmic pathologic examination, including immunohistochemistry.
RESULTS: The common splice-site altering synonymous variant c.3156C > T, p.(Gly1052=) in COL17A1 was confirmed in 15 individuals with ERED from the four families. Subepithelial corneal scarring grades varied and increased with age, leading to decreased best-corrected visual acuity. PTK improved vision in 58- and 67-year-old individuals without reactivating the disease. The keratectomy specimens showed an uneven epithelium and a spectrum of basement membrane abnormalities, including breaks, fragmentation, multiplication and entrapment within the subepithelial scar, reflecting recurrent erosions. The stromal cells consisted of varying proportions of bland and activated fibroblasts and myofibroblasts, reflecting different ages of scars. The family with the largest number of known affected generations originated from Southern Sweden.
CONCLUSIONS: The phenotype in the Finnish ERED families is consistent with earlier reports of the c.3156C > T variant, although the severity has varied between reports. The phenotype may be modulated by other genes. This study suggests a likely founder effect of the variant in both Finnish and Swedish populations due to their shared population histories. If vision is compromised, PTK can be considered especially in older patients.
METHODS: Eleven affected and two unaffected individuals underwent clinical ophthalmological examination, anterior segment photography, and corneal topography. Two of them underwent phototherapeutic keratectomy (PTK). Genetic analysis included both next-generation and Sanger sequencing. Specimens from the manual keratectomy of one patient were available for ophthalmic pathologic examination, including immunohistochemistry.
RESULTS: The common splice-site altering synonymous variant c.3156C > T, p.(Gly1052=) in COL17A1 was confirmed in 15 individuals with ERED from the four families. Subepithelial corneal scarring grades varied and increased with age, leading to decreased best-corrected visual acuity. PTK improved vision in 58- and 67-year-old individuals without reactivating the disease. The keratectomy specimens showed an uneven epithelium and a spectrum of basement membrane abnormalities, including breaks, fragmentation, multiplication and entrapment within the subepithelial scar, reflecting recurrent erosions. The stromal cells consisted of varying proportions of bland and activated fibroblasts and myofibroblasts, reflecting different ages of scars. The family with the largest number of known affected generations originated from Southern Sweden.
CONCLUSIONS: The phenotype in the Finnish ERED families is consistent with earlier reports of the c.3156C > T variant, although the severity has varied between reports. The phenotype may be modulated by other genes. This study suggests a likely founder effect of the variant in both Finnish and Swedish populations due to their shared population histories. If vision is compromised, PTK can be considered especially in older patients.
摘要：
目的：描述由XVII型胶原蛋白α1链基因（COL17A1）的致病变异c.3156C>T引起的上皮复发性糜烂营养不良（ERED）的四个芬兰家族。
方法：11名受影响的个体和2名未受影响的个体接受了临床眼科检查，眼前段摄影,和角膜地形图。其中两人接受了光疗角膜切除术（PTK）。遗传分析包括下一代和Sanger测序。一名患者的人工角膜切削术标本可用于眼科病理检查，包括免疫组织化学.
结果：常见剪接位点改变的同义变体c.3156C>T，在来自四个家庭的15个ERED个体中确认了COL17A1中的p。（Gly1052=）。上皮下角膜瘢痕分级随年龄变化而增加，导致最佳矫正视力下降。PTK改善了58岁和67岁个体的视力，而没有重新激活疾病。角膜切除术标本显示上皮不均匀和一系列基底膜异常，包括休息,碎片化,上皮下瘢痕内的增殖和截留，反映反复的侵蚀。基质细胞由不同比例的温和和活化的成纤维细胞和肌成纤维细胞组成，反映不同年龄的伤疤。已知受影响世代人数最多的家庭起源于瑞典南部。
结论：芬兰ERED家族的表型与早期报道的c.3156C>T变体一致，尽管不同报告的严重程度有所不同。表型可以由其他基因调节。这项研究表明，由于芬兰和瑞典人口的共同人口历史，该变体可能在芬兰和瑞典人口中产生创始人效应。如果视力受损，特别是在老年患者中可以考虑PTK。
方法：11名受影响的个体和2名未受影响的个体接受了临床眼科检查，眼前段摄影,和角膜地形图。其中两人接受了光疗角膜切除术（PTK）。遗传分析包括下一代和Sanger测序。一名患者的人工角膜切削术标本可用于眼科病理检查，包括免疫组织化学.
结果：常见剪接位点改变的同义变体c.3156C>T，在来自四个家庭的15个ERED个体中确认了COL17A1中的p。（Gly1052=）。上皮下角膜瘢痕分级随年龄变化而增加，导致最佳矫正视力下降。PTK改善了58岁和67岁个体的视力，而没有重新激活疾病。角膜切除术标本显示上皮不均匀和一系列基底膜异常，包括休息,碎片化,上皮下瘢痕内的增殖和截留，反映反复的侵蚀。基质细胞由不同比例的温和和活化的成纤维细胞和肌成纤维细胞组成，反映不同年龄的伤疤。已知受影响世代人数最多的家庭起源于瑞典南部。
结论：芬兰ERED家族的表型与早期报道的c.3156C>T变体一致，尽管不同报告的严重程度有所不同。表型可以由其他基因调节。这项研究表明，由于芬兰和瑞典人口的共同人口历史，该变体可能在芬兰和瑞典人口中产生创始人效应。如果视力受损，特别是在老年患者中可以考虑PTK。
