De Bonis Patrizia, Laborante Antonio, Pizzicoli Costantina, Stallone Raffaella, Barbano Raffaela, Longo Costanza, Mazzilli Emilio, Zelante Leopoldo, Bisceglia Luigi
Unità di Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Mol Vis. 2011;17:2482-94. Epub 2011 Sep 24.
To evaluate the involvement of Visual System Homeobox 1 (VSX1), Secreted Protein Acidic and Rich in Cysteine (SPARC), Superoxide Dismutase 1 (SOD1), Lysyl Oxidase (LOX), and Tissue Inhibitor of Metalloproteinase 3 (TIMP3) in sporadic and familial keratoconus.
Mutational analysis of the five genes was performed by sequencing and fragment analysis in a large cohort of 302 Italian patients, with a diagnosis of keratoconus based on clinical examination and corneal topography. The variants identified in VSX1 and SPARC were also assessed in the available relatives of the probands.
A novel mutation p.G239R and previously reported mutations were found in VSX1. Novel and already reported variants were identified in SPARC and SOD1, whose pathogenic significance has not been established. No pathogenic variants have been identified in LOX and TIMP3.
Molecular analysis of the five genes in a cohort of 225 sporadic and 77 familial keratoconus cases confirms the possible pathogenic role of VSX1 though in a small number of patients; a possible involvement of LOX and TIMP3 could be excluded; and the role played by SOD1 and SPARC in determining the disease as not been definitively clarified. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of the disease that in the authors' opinion, and according with several authors, should be considered as a complex disease.
评估视系统同源盒1（VSX1）、富含半胱氨酸的酸性分泌蛋白（SPARC）、超氧化物歧化酶1（SOD1）、赖氨酰氧化酶（LOX）和金属蛋白酶组织抑制剂3（TIMP3）在散发性和家族性圆锥角膜中的作用。
对302例意大利患者进行了这五个基因的突变分析，这些患者均根据临床检查和角膜地形图诊断为圆锥角膜。在这些先证者的亲属中也评估了VSX1和SPARC中鉴定出的变异。
在VSX1中发现了一个新的p.G239R突变和先前报道的突变。在SPARC和SOD1中鉴定出了新的和已报道的变异，但其致病意义尚未确定。在LOX和TIMP3中未鉴定出致病变异。
对225例散发性和77例家族性圆锥角膜病例的这五个基因进行分子分析，证实了VSX1可能的致病作用，尽管仅在少数患者中存在；可以排除LOX和TIMP3可能的作用；SOD1和SPARC在该疾病发生中的作用尚未明确阐明。需要进一步研究以确定其他参与该疾病发病机制和进展的重要遗传因素，作者认为，根据其他一些作者的观点，该疾病应被视为一种复杂疾病。
