Liskova Petra, Hysi Pirro G, Waseem Naushin, Ebenezer Neil D, Bhattacharya Shomi S, Tuft Stephen J
Division of Genetics, Institute of Ophthalmology, University College London, London, England.
Arch Ophthalmol. 2010 Sep;128(9):1191-5. doi: 10.1001/archophthalmol.2010.200.
To search for genetic factors that could increase susceptibility to keratoconus.
A single-nucleotide polymorphism chip method was used to generate whole-genome data in a multiethnic panel of 6 families with 3 to 5 members affected by keratoconus. Candidate gene screening was performed by direct sequencing.
Linkage analysis results were strongest for a locus on chromosome 14q24.3. This region contains a relatively small number of genes of potential interest, including VSX2, a homeobox gene known to be involved in eye development and implicated in a spectrum of ocular disorders. However, sequencing the coding region of VSX2 did not reveal a sequence variant segregating with disease in any of the families described.
To our knowledge, this is the first report of linkage for keratoconus to 14q24.3 and the region is likely to harbor important inheritable genetic factors that may affect susceptibility to keratoconus.
Further genetic research is needed to identify the genes responsible for keratoconus. This knowledge will aid in understanding the molecular pathophysiology of this condition and may lead to improved treatment strategies.
寻找可能增加圆锥角膜易感性的遗传因素。
采用单核苷酸多态性芯片方法，在一个由6个家庭组成的多民族小组中生成全基因组数据，每个家庭有3至5名成员患有圆锥角膜。通过直接测序进行候选基因筛选。
14号染色体q24.3位点的连锁分析结果最为显著。该区域包含相对较少数量的潜在相关基因，包括VSX2，这是一个已知参与眼睛发育并与一系列眼部疾病有关的同源框基因。然而，对VSX2编码区进行测序并未在所述的任何家庭中发现与疾病共分离的序列变异。
据我们所知，这是首次报道圆锥角膜与14q24.3的连锁关系，该区域可能含有影响圆锥角膜易感性的重要可遗传基因因素。
需要进一步的基因研究来确定导致圆锥角膜的基因。这些知识将有助于理解这种疾病的分子病理生理学，并可能带来改进的治疗策略。
