Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene
Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene
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DOI：
10.1167/iovs.04-0804
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Boman, H
中科院分区：
文献类型：
--
作者：
Bredrup, C;Knappskog, PM;Boman, H
目的。描述一个先天性角膜间质营养不良家族的临床和病理特征，并确定这种疾病的遗传基础。家族三代成员均接受眼科检查。用透射电镜观察保存的角膜扣。分子遗传学研究，包括微卫星标记全基因组扫描、连锁分析和DNA测序。营养不良以常染色体显性模式遗传，出生后不久可见混浊的角膜。没有相关的系统性异常或先天性疾病。穿透性角膜移植术（PK）后，56%的眼睛移植物完全清除，平均（范围）观察期为19.5年（3 - 36）。透射电镜下角膜扣显示胶原原纤维排列正常的片层，被异常的纤维层隔开。全基因组筛选显示与12q22染色体连锁，D12S351位点的最大LOD评分为4.68。随后的候选基因测序显示编码decorin的DCN基因（c.967delT）发生移码突变，预测decorin蛋白的c端截断（p.S323fsX5）。作者推测，截短的decorin以不理想的方式与胶原蛋白结合，扰乱了角膜胶原纤维形成的规律性，从而导致角膜混浊。据作者所知，这是第一次描述与人类decorin基因遗传改变相关的疾病。
PURPOSE. To describe the clinical and pathologic characteristics of a family with a congenital stromal dystrophy of the cornea and to identify the genetic basis for this disorder.METHODS. All family members in three generations underwent ophthalmic examination. Stored corneal buttons were examined by transmission electron microscopy. Molecular genetic studies, including a genome-wide scan with microsatellite markers, linkage analysis, and DNA sequencing, were performed.RESULTS. The dystrophy was inherited in an autosomal dominant pattern and was seen as clouded corneas shortly after birth. No associated systemic abnormalities or congenital diseases were present. After penetrating keratoplasty (PK), the grafts remained completely clear in 56% of the eyes with a mean ( range) observation period of 19.5 years ( 3 - 36). Transmission electron microscopy of corneal buttons revealed lamellae with normal arrangement of collagen fibrils separated by abnormal fibrillar layers. Genome-wide screening revealed linkage to chromosome 12q22, with a maximum LOD score of 4.68 at D12S351. Subsequent sequencing of candidate genes revealed a frameshift mutation in the DCN gene (c.967delT) that encodes for decorin, predicting a C-terminal truncation of the decorin protein (p.S323fsX5).CONCLUSIONS. The authors hypothesize that truncated decorin binds to collagen in a suboptimal way, disturbing the regularity of corneal collagen fibril formation and thereby causing corneal opacities. To the best of the authors' knowledge, this is the first description of a disorder associated with an inherited alteration in the decorin gene in humans.