Liskova Petra, Ebenezer Neil D, Hysi Pirro G, Gwilliam Rhian, El-Ashry Mohamed F, Moodaley Lalitha C, Hau Scott, Twa Michael, Tuft Stephen J, Bhatacharya Shomi S
Division of Molecular Genetics, Institute of Ophthalmology, UCL, London, UK.
Mol Vis. 2007 Oct 4;13:1887-91.
To evaluate the role of the visual system homeobox gene 1 (VSX1) in the pathogenesis of familial keratoconus.
Families with two or more individuals with keratoconus were recruited and their members examined. The coding region and intron-exon junctions of the VSX1 gene were sequenced in affected individuals. In cases where there were possible pathogenic changes, segregation within the pedigree was analyzed. Meta analysis of reports on an association of p.D144E change with keratoconus phenotype was performed.
Probands from a panel of 85 apparently unrelated keratoconus families were included. Eleven sequence variants were observed, including the previously reported c.432C>G (p.D144E) change and two novel intronic single nucleotide polymorphisms. However, these three changes did not cosegregate with the disease phenotype.
We excluded the c.432C>G sequence alteration as the direct cause of the disease. Lack of possibly pathogenic VSX1 sequence variants in the familial panel suggests that involvement of this gene in the pathogenesis of keratoconus is likely to be confined to a small number of pedigrees, at least in the population studied.
评估视觉系统同源盒基因1（VSX1）在家族性圆锥角膜发病机制中的作用。
招募有两名或更多圆锥角膜患者的家族，并对其成员进行检查。对患病个体的VSX1基因编码区和内含子-外显子连接区进行测序。对于存在可能致病变化的情况，分析家系中的分离情况。对关于p.D144E变化与圆锥角膜表型关联的报告进行荟萃分析。
纳入了来自85个明显无亲缘关系的圆锥角膜家族的先证者。观察到11个序列变异，包括先前报道的c.432C>G（p.D144E）变化和两个新的内含子单核苷酸多态性。然而，这三个变化并未与疾病表型共分离。
我们排除了c.432C>G序列改变作为该疾病的直接病因。家族性样本中缺乏可能致病的VSX1序列变异表明，该基因在圆锥角膜发病机制中的作用可能仅限于少数家系，至少在所研究的人群中如此。
