Disruption of OVOL2 Distal Regulatory Elements as a Possible Mechanism Implicated in Corneal Endothelial Dystrophy
Disruption of OVOL2 Distal Regulatory Elements as a Possible Mechanism Implicated in Corneal Endothelial Dystrophy
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OVOL2 远端调节元件的破坏是角膜内皮营养不良的可能机制
DOI：
10.1155/2024/4450082
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发表时间：
2024
期刊：
影响因子：
3.9
通讯作者：
Dudakova L
中科院分区：
文献类型：
--
作者：
Dudakova L
角膜内皮营养不良的遗传结构在相当数量的受影响个体中仍然未知。本研究中的先证者在新生儿期被诊断为原发性内皮细胞功能障碍导致的双侧角膜混浊。他的父母和姐姐都没有角膜疾病的迹象。常规核型分析显示3号和20号染色体t（3;20）（q25;p11 - 12）发生了新易位。在基因组和靶向桑格测序分析后，在核苷酸水平上定位断裂点。值得注意的是，20号染色体上的断点被鉴定为与角膜内皮营养不良相关基因OVOL 2位于相同的拓扑相关结构域（topologically associated domain，简称OVOL 2）内，并且预计它会破坏远端增强子。3号染色体上的断裂点位于PFN 2的内含子2内，其目前与任何人类疾病无关。对先证者基因组的进一步询问未能在角膜内皮营养不良相关基因中鉴定出任何其他潜在的致病性变体。OVOL 2易位到新的基因组环境中诱导的念珠菌感染调控元件和/或位置效应的破坏可能导致OVOL 2表达异常，这是角膜内皮营养不良的一种先前表征的疾病机制。进一步的研究是必要的，以探讨如何破坏调控元件可能阐明遗传未解决的角膜内皮营养不良。
The genetic architecture of corneal endothelial dystrophies remains unknown in a substantial number of affected individuals. The proband investigated in the current study was diagnosed in the neonatal period with bilateral corneal opacification due to primary endothelial cell dysfunction. Neither his parents nor his sister had signs of corneal disease. Conventional karyotyping revealed ade novotranslocation involving chromosomes 3 and 20, t(3;20)(q25;p11‐12). Following genome and targeted Sanger sequencing analysis, the breakpoints were mapped at the nucleotide level. Notably, the breakpoint on chromosome 20 was identified to lie within the same topologically associated domain (TAD) as corneal endothelial dystrophy‐associated geneOVOL2, and it is predicted to disrupt distal enhancers. The breakpoint at chromosome 3 is located within intron 2 ofPFN2, which is currently not associated with any human disease. Further interrogation of the proband’s genome failed to identify any additional potentially pathogenic variants in corneal endothelial dystrophy‐associated genes. Disruption of a candidatecis‐regulatory element and/or positional effects induced by translocation ofOVOL2to a novel genomic context may lead to an aberrantOVOL2expression, a previously characterized disease mechanism of corneal endothelial dystrophy. Further research is necessary to explore how disruption of regulatory elements may elucidate genetically unsolved corneal endothelial dystrophies.
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影响因子：
5.2
作者：
Liskova, Petra;Evans, Cerys J.;Hardcastle, Alison J.
通讯作者：
Hardcastle, Alison J.
三种不同设备在健康眼睛中获得的眼前节测量结果的比较
影响因子：
--
作者：
C. López de la Fuente;A. Sánchez;F. Segura;I. Pinilla
通讯作者：
I. Pinilla
影响因子：
3.1
作者：
Ozyol E;Özyol P
通讯作者：
Özyol P
影响因子：
3.4
作者：
Dudakova, Lubica;Evans, Cerys J.;Liskova, Petra
通讯作者：
Liskova, Petra
影响因子：
5.5
作者：
Ogando, Diego G.;Jalimarada, Supriya S.;Bonanno, Joseph A.
通讯作者：
Bonanno, Joseph A.