PAX6 allelic heterogeneity in Mexican congenital aniridia patients: expanding the mutational spectrum with seven novel pathogenic variants
PAX6 allelic heterogeneity in Mexican congenital aniridia patients: expanding the mutational spectrum with seven novel pathogenic variants
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DOI：
10.1111/ceo.12982
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Carlos Zenteno, Juan
中科院分区：
文献类型：
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作者：
Perez-Solorzano, Sofia;Chacon-Camacho, Oscar F.;Carlos Zenteno, Juan
ImportanceThe重要性的研究是描述墨西哥患者的临床特征和突变分析与aniridia.BackgroundAniridia是一种全眼遗传性眼病引起的PAX 6转录因子突变。突变检测率在不同人群中变化很大，从30%到90%不等。关于墨西哥无虹膜患者PAX 6突变分析的研究很少。为了在该国建立更具代表性的PAX 6突变频率，本研究分析了22名墨西哥无虹膜先证者及其亲属，采用Sanger测序法对PAX 6基因所有编码外显子和侧翼内含子区进行突变分析。PAX 6突变分析的特点和结果在先证者与无虹膜和可用的家庭members.ResultsPAX6在22个索引无虹膜的情况下允许识别的16个不同的突变。这些致病性变体中有7种是新的，包括c.183C>G，p. (Y61* ）; c.718delC，p.（R240Efs*3）; c.1149_1152delTCAG，p.（P385Wfs*139）; c.257_266delAAATAGCCCA，p.（K86Sfs*35）; c.836_843dupGCAACACA p.（P282Afs*86）; c.1032+2_1032+3insT;和c.141+2T>A。结论和相关性本系列的突变诊断率为77%，与其他人群的报道具有可比性。重要的是，在该病例系列中未发现创始者突变。我们的研究结果在无虹膜相关突变谱中增加了7种新的PAX 6致病性变体，并揭示了该人群中相当大的PAX 6等位基因异质性。
ImportanceThe importance of the study was to describe the clinical characteristics and mutational analysis of Mexican patients with aniridia.BackgroundAniridia is a panocular hereditary eye disease caused by mutations in the PAX6 transcription factor. Mutation detection rate is highly variable ranging from 30% to 90% in different populations. Very few studies have been published about the PAX6 mutational analysis in aniridia patients from Mexico. In order to establish a more representative PAX6 mutational frequency in the country, a cohort of 22 Mexican unrelated aniridia probands were analysed in this study.DesignCase series.ParticipantsA total of 22 Mexican probands with bilateral isolated aniridia and their available relatives were included.MethodsSanger sequencing was used for the mutational analysis of all coding exons and flanking intronic regions of PAX6.Main Outcome MeasuresClinical characteristics and results of PAX6 mutational analysis in probands with aniridia and available family members.ResultsMolecular analysis of PAX6 in 22 index cases with aniridia allowed the identification of a total of 16 different mutations. Seven of these pathogenic variants are novel, including c.183C>G, p.(Y61*); c.718delC, p.(R240Efs*3); c.1149_1152delTCAG, p.(P385Wfs*139); c.257_266delAAATAGCCCA, p.(K86Sfs*35); c.836_843dupGCAACACA p.(P282Afs*86); c.1032+2_1032+3insT; and c.141+2T>A. Inter and intrafamilial phenotypic heterogeneity was found.Conclusions and RelevanceThe mutational diagnostic rate in this series was 77%, which is comparable with reports from other populations. Importantly, no founder mutations were identified in this case series. Our results add 7 novel PAX6 pathogenic variants to the aniridia-related mutational spectrum and reveal considerable PAX6 allelic heterogeneity in this population.