一个碱基在 miR-184 的种子区发生单点突变会导致 EDICT 综合征。
A single-base substitution in the seed region of miR-184 causes EDICT syndrome.
机构信息
Center for Corneal Genetics, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
出版信息
Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):348-53. doi: 10.1167/iovs.11-8783.
PURPOSE
To investigate the cause of the syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT).
METHODS
Previously a multigenerational family was reported that comprised 10 individuals affected by syndromal anterior segment dysgenesis. Blood samples were re-collected from eight affected and two unaffected individuals, and genomic DNA was extracted. A total of 24 candidate genes and 4 microRNAs residing within the critical interval were sequenced bidirectionally. In silico analyses were performed to examine the effect of the causal variant on the stability of the pre-microRNA structure.
RESULTS
Bidirectional sequencing identified the single-base substitution +57C>T in miR-184. This variation segregated with the disease phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes, and 28 nonhuman vertebrates.
CONCLUSIONS
The single-base-pair substitution in the seed region of miR-184 is responsible for the disease phenotype observed in EDICT syndrome.
目的
探讨以血管内皮营养不良、虹膜发育不全、先天性白内障和基质变薄为特征的综合征（EDICT）的病因。
方法
先前曾报道过一个多代家族，该家族由 10 名受综合征性前节发育不良影响的个体组成。从 8 名受影响者和 2 名未受影响者重新采集血样，并提取基因组 DNA。对 24 个候选基因和位于关键区间内的 4 个 microRNA 进行了双向测序。通过计算机模拟分析，研究了致病变异对 pre-microRNA 结构稳定性的影响。
结果
双向测序确定了 miR-184 中+57C>T 的单碱基替换。该变异与疾病表型相关，在 1000 基因组计划、1130 个对照染色体和 28 种非人类脊椎动物中均不存在。
结论
miR-184 种子区的单碱基替换是导致 EDICT 综合征中观察到的疾病表型的原因。
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