In Vivo Laser Confocal Microscopy Findings and Mutational Analysis for Schnyder's Crystalline Corneal Dystrophy
In Vivo Laser Confocal Microscopy Findings and Mutational Analysis for Schnyder's Crystalline Corneal Dystrophy
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DOI：
10.1016/j.ophtha.2008.12.042
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发表时间：
2009-06-01
期刊：
影响因子：
13.7
通讯作者：
Sugiyama, Kazuhisa
中科院分区：
文献类型：
--
作者：
Kobayashi, Akira;Fujiki, Keiko;Sugiyama, Kazuhisa
目的：鉴定日本施奈德晶体角膜营养不良 (SCCD) 患者的 UbiA 异戊二烯基转移酶结构域蛋白 I (UBIAD1) 基因是否存在突变，并使用激光扫描共聚焦显微镜（Heidelberg Retina Tomograph 2 Rostock Cornea Module；Heidelberg Engineering GmbH，Dossenheim，德国）研究体内微观结构表型和基因型相关性。 设计：小型比较病例系列。 参与者：来自 3 个临床诊断 SCCD 家系的 3 名患者（3 名男性）及其亲属（2 名男性，1 名女性）参与本研究。 测试： 所有参与者均进行基因检查、裂隙灯生物显微镜检查和活体激光共聚焦显微镜检查。 主要结果指标： 从患者和 100 名无关健康志愿者的血液样本中分离基因组 DNA（200 条染色体），用于突变筛查UBIAD1基因。对选定的角膜层共焦图像的沉积物的形状和光反射程度进行定性评估。结果：鉴定出 UBIAD1 基因（Y174C、K181R 和 N233H）的新突变。此外，在1个家系中证实了突变（Y174C）和SCCD的共分离，表明UBIAD1基因的突变是SCCD的病因。所有 200 条对照染色体中均不存在这 3 个突变。体内激光共聚焦显微镜观察4例上皮下高反射晶体；晶体形状为针状（3例）或长方形（1例）。 1个家系中显示出表型和基因型相关性，1个家系中也显示出表型异质性（SCCD有或没有由UBIAD1基因中相同的Y174C突变引起的晶体）。结论：在3个不相关的日本SCCD家系中检测到了UBIAD1基因的非同义新突变，证实了该疾病的遗传异质性。体内激光共焦显微镜能够以高分辨率识别与基因图谱 SCCD 相关的特征性角膜微结构变化，并呈现表型异质性。需要使用大量 SCCD 患者进行进一步的共聚焦和突变分析，以阐明体内微观结构表型和基因型相关性。 财务披露：作者对本文讨论的任何材料没有专有或商业利益。眼科 2009；116：1029-1037 (C) 2009 年，美国眼科学会。
Objective: To identify any mutation of the UbiA prenyltransferase domain-containing protein I (UBIAD1) gene in Japanese patients with Schnyder's crystalline corneal dystrophy (SCCD) and to investigate in vivo microstructural phenotype and genotype correlations using laser scanning confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module; Heidelberg Engineering GmbH, Dossenheim, Germany).Design: Small, comparative case series.Participants: Three patients from 3 pedigrees (3 males) with clinically diagnosed SCCD and their relatives (2 males, 1 female) participated in this study.Testing: All participants were examined genetically and by slit-lamp biomicroscopy and in vivo laser confocal microscopy.Main Outcome Measures: Genomic DNA from the patients and 100 unrelated healthy volunteers (200 chromosomes) was isolated from blood samples and used for mutation screening of the UBIAD1 gene. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of deposits. Results: Novel mutations in the UBIAD1 gene (Y174C, K181R, and N233H) were identified. Additionally, cosegregation of the mutation (Y174C) and SCCD was confirmed in 1 pedigree, indicating that the mutation of the UBIAD1 gene is causative for SCCD. The 3 mutations were absent in all 200 control chromosomes. In vivo laser confocal microscopy demonstrated subepithelial highly reflective crystals in 4 cases; the shapes of the crystals were needle-shaped (3 cases) or rectangular (1 case). A phenotype and genotype correlation was demonstrated in 1 pedigree, and phenotypic heterogeneity (SCCD with or without crystals caused by a same mutation of Y174C in the UBIAD1 gene) also was demonstrated in 1 pedigree.Conclusions: Nonsynonymous novel mutations in the UBIAD1 gene were detected in 3 unrelated Japanese pedigrees with SCCD, confirming the genetic heterogeneity of this disorder. In vivo laser confocal microscopy is capable of identifying characteristic corneal microstructural changes related to genetically mapped SCCD with high resolution, and phenotypic heterogeneity was presented. Further confocal and mutational analysis using a larger number of patients with SCCD is required to elucidate in vivo microstructural phenotype and genotype correlations.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:1029-1037 (C) 2009 by the American Academy of Ophthalmology.