Evidence against ZNF469 being causative for keratoconus in Polish patients
Evidence against ZNF469 being causative for keratoconus in Polish patients
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DOI：
10.1111/aos.12968
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发表时间：
2016-05-01
影响因子：
3.4
通讯作者：
Gajecka, Marzena
中科院分区：
文献类型：
--
作者：
Karolak, Justyna A.;Gambin, Tomasz;Gajecka, Marzena
圆锥角膜（KTCN）是一种以角膜基质变薄和前突为特征的退行性疾病，可导致严重的视功能损害。最近的一项研究提出，在ZNF 469罕见的杂合突变决定KTCN aetiology.MethodsTo调查的贡献ZNF 469 KTCN，我们桑格测序了42名不相关的波兰KTCN患者和49名波兰高度近视（HM）患者的ZNF 469，并将结果与全外显子组测序（WES）进行了比较。在268名没有眼部异常的波兰个体中进行的数据。结果对于患有KTCN和HM的个体，ZNF 469非同义变异体的平均数目为16.31和16.0，（p=0.3724）。所有已识别的变体均已报告。根据WES结果确定备选等位基因频率（AAF）。在错义变异体中，只有一个（rs528085780）具有AAF 0.001，并在一名散发性KTCN患者中鉴定。然而，由此产生的Arg1864Lys取代并没有被预测是有害的。ConclusionIn总结，我们还没有发现一个显着丰富的序列变异ZNF 469在波兰患者KTCN。在我们的KTCN组中鉴定的ZNF 469变体的高患病率是在一般人群中观察到的常见遗传变异的典型。我们的研究结果表明，ZNF 469的变异与KTCN无关，其他遗传变异与波兰患者的这种疾病的发展和进展有关。
PurposeKeratoconus (KTCN) is a degenerative disorder characterized by stromal thinning and protrusion of the cornea, resulting in severe impairment of visual function. A recent study proposed that rare heterozygous mutations in ZNF469 determine KTCN aetiology.MethodsTo investigate the contribution of ZNF469 to KTCN, we Sanger sequenced ZNF469 in 42 unrelated Polish patients with KTCN and 49 Polish individuals with high myopia (HM) and compared the results with whole-exome sequencing (WES) data performed in 268 Polish individuals without ocular abnormalities.ResultsThe average number of ZNF469 non-synonymous variants was 16.31 and 16.0 for individuals with KTCN and HM, respectively (p=0.3724). All identified variants were previously reported. Alternative allele frequency (AAF) was determined based on the WES results. Among missense variants, only one (rs528085780) has AAF0.001 and was identified in one patient with sporadic KTCN. However, the resulting Arg1864Lys substitution was not predicted to be deleterious.ConclusionIn summary, we have not found a significant enrichment of sequence variants in ZNF469 in Polish patients with KTCN. High prevalence of ZNF469 variants identified in our KTCN group is typical for a common genetic variation observed in general population. Our findings indicate that variation in ZNF469 is not responsible for KTCN and other genetic variants are involved in the development and progression of this disease in Polish patients.