Bisceglia Luigi, Ciaschetti Marilena, De Bonis Patrizia, Campo Pablo Alberto Perafan, Pizzicoli Costantina, Scala Costanza, Grifa Michele, Ciavarella Pio, Delle Noci Nicola, Vaira Filippo, Macaluso Claudio, Zelante Leopoldo
Medical Genetics Service and Ophthalmology Department, IRCCS-CSS Hospital, San Giovanni Rotondo (Fg), Italy.
Invest Ophthalmol Vis Sci. 2005 Jan;46(1):39-45. doi: 10.1167/iovs.04-0533.
Keratoconus is a noninflammatory corneal disorder that is clinically and genetically heterogeneous. Mutations in the VSX1 (visual system homeobox 1) gene have been identified for two distinct, inherited corneal dystrophies: posterior polymorphous corneal dystrophy and keratoconus. To evaluate the possible role of the VSX1 gene in a series of Italian patients, 80 keratoconus-affected subjects were screened for mutations.
The diagnosis of keratoconus was made on the basis of clinical examination and corneal topography. The whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing.
Three already-described changes, D144E, G160D, and P247R, and a novel L17P mutation were found in 7 of 80 unrelated patients (8.7%). Two undescribed intronic polymorphisms are also reported.
Mutational analysis of the VSX1 gene in a series of Italian patients revealed one novel mutation and confirmed an important role played by this gene in a significant proportion of patients affected by keratoconus, when it is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance.
圆锥角膜是一种非炎性角膜疾病，在临床和遗传方面具有异质性。已确定VSX1（视觉系统同源盒1）基因突变与两种不同的遗传性角膜营养不良有关：后极性多形性角膜营养不良和圆锥角膜。为了评估VSX1基因在一系列意大利患者中的可能作用，对80名圆锥角膜患者进行了突变筛查。
根据临床检查和角膜地形图诊断圆锥角膜。通过直接测序分析VSX1基因的整个编码区和外显子-内含子连接区。
在80名无亲缘关系的患者中有7名（8.7%）发现了3种已报道的变异，即D144E、G160D和P247R，以及一种新的L17P突变。还报告了两种未描述的内含子多态性。
对一系列意大利患者的VSX1基因进行突变分析，发现了一种新的突变，并证实当该基因作为常染色体显性性状以可变表达和不完全外显率遗传时，在相当一部分圆锥角膜患者中发挥重要作用。
