In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy
In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy
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DOI：
10.1007/s10384-018-00643-6
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Sugiyama, Kazuhisa
中科院分区：
文献类型：
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作者：
Nishino, Tsubasa;Kobayashi, Akira;Sugiyama, Kazuhisa
目的报道Meesmann角膜营养不良的基因突变分析和活体组织学。研究设计前瞻性病例对照研究。方法选择临床诊断为Meesmann角膜营养不良的3个家系的6例患者。对选定的患者进行了裂隙灯生物显微镜、眼前段光学相干断层扫描(AS-OCT)和活体激光共聚焦显微镜(IVCM)检查。对所有6名患者和选定的未受影响的家庭成员进行角蛋白基因KRT3和KRT12的突变筛查。结果在所有受影响的个体中，荧光灯生物显微镜显示出大量的上皮内微囊。AS-OCT显示高反射率和高角膜上皮层厚度(平均64.8m)，所有受试者(3/3)。IVCM可见角膜基质层多发上皮微囊及高反光物质(6/6)、上皮下神经异常(6/6)、细小点状高反光物质(6/6)、针状高反光物质(4/6)。在所有6名患者中都发现了KRT12基因(c.394C>；G，p.L132V)的杂合基因突变。结论我们在6例日本遗传性Meesmann角膜营养不良患者中发现了KRT12基因的杂合突变(c.394C>；G，p.L132V)。这是首次在日本Meesmann角膜营养不良患者中证实这种基因突变的研究。这种突变已经在一名美国Meesmann角膜营养不良患者中独立报道，证实了它的致病性。AS-OCT和IVCM被证明是观察这种营养不良的角膜上皮层病理的有用工具。此外，IVCM还显示了在此营养不良中未见报道的角膜基质层病变。
PurposeTo report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy.Study designProspective, case control study.MethodsSix patients from three independent families with clinically diagnosed Meesmann corneal dystrophy were enrolled in this study. Slit-lamp biomicroscopy with fluorescein vital staining, anterior segment optical coherence tomography (AS-OCT), and in vivo laser confocal microscopy (IVCM) were performed on selected patients. Mutational screening for the keratin genes KRT3 and KRT12 was performed in all six patients and selected unaffected family members.ResultsSlit-lamp biomicroscopy revealed numerous intraepithelial microcysts in all affected individuals. AS-OCT revealed hyperreflectivity and high corneal epithelial layer thickness (mean, 64.8m) in all individuals tested (3/3). By using IVCM, multiple epithelial microcysts and hyperreflective materials (6/6), subepithelial nerve abnormalities (6/6), tiny punctate hyperreflective material (6/6), and needle-like hyperreflective materials (4/6) were observed in the corneal stromal layer. A heterozygous genetic mutation in the KRT12 gene (c.394 C>G, p.L132V) was identified in all six patients. No pathological mutation was observed in the KRT3 gene.ConclusionWe identified a heterozygous genetic mutation (c.394 C>G, p.L132V) in the KRT12 gene in six Japanese patients with inherited Meesmann corneal dystrophy. This is the first study to confirm this genetic mutation in Japanese Meesmann corneal dystrophy patients. This mutation has been independently reported in an American Meesmann corneal dystrophy patient, confirming its pathogenicity. AS-OCT and IVCM proved to be useful tools for observing corneal epithelial layer pathology in this dystrophy. Furthermore, IVCM reveals corneal stromal layer pathological changes not previously reported in this dystrophy.