A Cohesin Subunit Variant Identified from a Peripheral Sclerocornea Pedigree
A Cohesin Subunit Variant Identified from a Peripheral Sclerocornea Pedigree
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从周围巩膜谱系中鉴定出的粘连蛋白亚基变体
DOI：
10.1155/2019/8781524
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发表时间：
2019-11-12
期刊：
影响因子：
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通讯作者：
Chu, Wai Kit
中科院分区：
文献类型：
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作者：
Zhang, Bi Ning;Chan, Tommy Chung Yan;Chu, Wai Kit
背景：角膜硬化症是一种罕见的先天性疾病，以角膜混浊为主要特征。在这里，我们报告了一个非血缘的中国家庭与多个周边巩膜患者跨越三代遗传的常染色体显性遗传方式。方法回顾性分析一个周边性角膜硬化症家系。对14名家系成员进行了全面的眼科检查和评估。使用全外显子组测序来鉴定受影响谱系成员的遗传改变。使用来自家族成员的血液样品建立淋巴母细胞样细胞系（LCL）。用这些细胞系进行功能测试。结果对一个周边性巩膜炎家系的6名患眼和8名非患眼进行了检查。所有受影响的个体都表现出双眼周边角膜的硬化特征。平均水平和垂直角膜直径被发现显着减少在受影响的成员。受影响和未受影响的受试者之间的平均心尖测厚也观察到显著差异。这些眼科参数与平坦角膜的参数不同。通过全外显子组测序鉴定RAD21C1348T变体。虽然这种变体导致分离酶切割位点的RAD21 R450C取代，但来自周边巩膜家族成员的细胞没有有丝分裂和倍性缺陷。结论我们报告了一个与扁平角膜无关的周边型巩膜病家系。发现一种RAD21变异体与周边巩膜共分离。我们的研究结果表明，RAD 21的功能，而不是其细胞周期和染色体分离的调节，可以强调周边巩膜的发病机制。
Background Sclerocornea is a rare congenital disorder characterized with the opacification of the cornea. Here, we report a nonconsanguineous Chinese family with multiple peripheral sclerocornea patients spanning across three generations inherited in an autosomal dominant manner. Methods This is a retrospective case series of a peripheral sclerocornea pedigree. Comprehensive ophthalmic examinations were conducted and assessed on 14 pedigree members. Whole-exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from the family members. Functional tests were performed with these cell lines. Results Six affected and eight unaffected members of a family with peripheral sclerocornea were examined. All affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were found significantly decreased in the affected members. Significant differences were also observed on the mean apex pachymetry between affected and unaffected subjects. These ophthalmic parameters did not resemble that of cornea plana. A RAD21C1348T variant was identified by whole-exome sequencing. Although this variant causes RAD21 R450C substitution at the separase cleavage site, cells from peripheral sclerocornea family members had no mitosis and ploidy defects. Conclusion We report a family of peripheral sclerocornea with no association with cornea plana. A RAD21 variant was found cosegregating with peripheral sclerocornea. Our results suggest that RAD21 functions, other than its cell cycle and chromosome segregation regulations, could underline the pathogenesis of peripheral sclerocornea.