Novel CHST6 gene mutations in 2 unrelated cases of macular corneal dystrophy.
Novel CHST6 gene mutations in 2 unrelated cases of macular corneal dystrophy.
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DOI：
10.1097/ico.0b013e3182012888
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发表时间：
2011-06
期刊：
影响因子：
2.8
通讯作者：
Huang AJ
中科院分区：
文献类型：
--
作者：
Patel DA;Harocopos GJ;Chang SH;Vora SC;Lubniewski AJ;Huang AJ
研究两例无关的黄斑角膜营养不良（MCD）患者碳水化合物硫转移酶6 （CHST6）基因可能的突变，并报道其中一例不典型间质沉积。角膜组织用抗硫酸角蛋白（KS）、抗转化生长因子β 1诱导蛋白（TGFBIp）、硫黄素-t、阿利新蓝和马松三色染色。测序确定CHST6基因和TGFBI基因第4和第12外显子的潜在突变。阿利新蓝染色显示存在多个上皮下和间质内粘多糖沉积，证实了两例MCD的诊断。病例1的免疫荧光染色显示仅在角化细胞和部分内皮细胞中存在硫酸化KS，与MCD IA型一致。在病例2中，在角化细胞和细胞外基质中观察到硫酸化KS的优先表达，与MCD II型一致。在病例1中观察到非典型亚上皮和浅表间质沉积，阿利新蓝、伊红、马松三色和硫黄- t染色阳性，表明存在透明质和淀粉样物质。CHST6基因测序结果显示，病例1中存在两个杂合突变（p.a g211gln和p.a g177gly突变），病例2中存在p.p pro186arg纯合突变。病例1 TGFBI基因外显子4、12均未发现突变。继发性透明质病和淀粉样变发生在MCD IA型患者中，CHST6中存在一种新的p.a g177gly突变。在非裔美国人的CHST6中，一种新的p.Pro186Arg突变与II型MCD有关。
To investigate possible mutations in the carbohydrate sulfotransferase 6 (CHST6) gene of two unrelated cases of macular corneal dystrophy (MCD) and to report atypical stromal deposits in one of them. Corneal tissues were stained with anti-sulfated keratan sulfate (KS), anti-transforming growth factor beta 1-induced protein (TGFBIp), thioflavin-T, alcian blue, and Masson trichrome. Sequencing was performed to identify potential mutations in the CHST6 gene and the fourth and twelfth exons of the TGFBI gene. Alcian blue staining revealed the presence of multiple subepithelial and intra-stromal mucopolysaccharide deposits, confirming the diagnosis of MCD in both cases. Immunofluorescence staining in case 1 revealed the presence of sulfated KS only in the keratocytes and select endothelial cells, consistent with MCD type IA. Preferential expression of sulfated KS was observed in keratocytes and extracellular stromal matrix in case 2, consistent with MCD type II. Atypical sub-epithelial and superficial stromal deposits were observed in case 1, which stained positively with alcian blue, eosin, Masson trichrome and thioflavin-T indicating the presence of hyaline and amyloid materials. CHST6 gene sequencing revealed two heterozygous mutations in case 1 (a p.Arg211Gln and a novel mutation of p.Arg177Gly) and a novel homozygous mutation of p.Pro186Arg in case 2. No mutations were found in exons 4 or 12 of the TGFBI gene in case 1. Secondary hyalinosis and amyloidosis occur in a case of MCD type IA with a novel p.Arg177Gly mutation in CHST6. A novel p.Pro186Arg mutation in CHST6 is associated with MCD type II in an African American.