Phenotype and genotype analysis in patients with macular corneal dystrophy
Phenotype and genotype analysis in patients with macular corneal dystrophy
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DOI：
10.1136/bjophthalmol-2014-305098
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发表时间：
2014-11-01
影响因子：
4.1
通讯作者：
Puzzolo, Domenico
中科院分区：
文献类型：
--
作者：
Nowinska, Anna K.;Wylegala, Edward;Puzzolo, Domenico
目的本研究的目的是分析角膜形态组织和识别突变的碳水化合物磺基转移酶6基因（CHST 6）的患者与黄斑角膜营养不良起源于波兰population.Methods的基础上裂隙灯检查，共聚焦显微镜，1310 nm时域和840 nm光谱域光学相干断层扫描诊断为黄斑角膜营养不良24例。从穿透性角膜移植术中获得的10个角膜按钮进行光学显微镜处理。CHST 6基因的遗传分析进行，其次是测序结果的研究。结果高反射，弥漫性角膜存款和反射率的普遍增加，揭示与光学相干断层扫描和共聚焦显微镜。这些沉积物从Bowman层延伸到后弹力层，并与基质角膜细胞内和周围的Alcian蓝阳性颗粒-丝状物质相关，这一点通过角膜按钮的结构分析得到证实。基因分析结果显示，该家系存在P64 L（杂合型）、Y110 C（纯合型）、R162 G和L200 R、M1L（杂合型和纯合型）等新突变和单核苷酸多态性。在体内角膜形态学评估或组织学分析中，未发现患者的表型异质性。
Aim The aim of this study was to analyse corneal morphological organisation and identify mutations in the carbohydrate sulfotransferase 6 gene (CHST6) in patients with macular corneal dystrophy originating in a Polish population.Methods Macular corneal dystrophy was diagnosed in 24 patients based on the slit-lamp exam, confocal microscopy, 1310 nm time domain and 840 nm spectral domain optical coherence tomography. 10 corneal buttons obtained from penetrating keratoplasty were processed for light microscopy. Genetic analysis of the CHST6 gene was performed, followed by a study of the sequencing results.Results Highly reflective, diffuse corneal deposits and a general increase in reflectivity were revealed with optical coherence tomography and confocal microscopy. The deposits extended from the Bowman layer to the Descemet membrane and correlated with the Alcian blue-positive granular-filamentous material into and around the stromal keratocytes confirmed by structural analysis of the corneal buttons. The genetic analysis of the blood samples identified the following mutations and single nucleotide polymorphisms: novel P64L (heterozygous), Y110C (homozygous), R162G and L200R, and M1L (heterozygous and homozygous).Conclusions Genetic mutation heterogeneity was revealed. No phenotype heterogeneity was revealed among patients with in vivo corneal morphology assessment or histological analysis.