PDF(Pubmed)
Abstract：
Inherited retinal dystrophies (IRDs) include a large chronic heterogeneity genetic disease. While many disease-causing pathogenic variants were involved in the progression of IRD, the Ceramide Kinase Like (CERKL) gene variant in Iranian patients is not well characterized. In this study, a consanguineous Iranian family with three generations was recruited whom presented with the clinical diagnosis of autosomal recessive IRD. By targeted next-generation sequencing (TGS) and Sanger sequencing, the proband was found to have a novel, pathological homozygous deletion variant c.560_568del (p.187_190del) of the CERKL gene (NM_001030311.2) that co-segregated with the disease in all affected family members. The Cerkl is highly expressed in the later four developmental retinal stages, playing a vital role in retina degeneration. Therefore, the identification of a novel, homozygous deletion CERKL variant c.560_568del (p.187_190del) in an IRD familial cohort descent provides insights into the molecular pathogenesis of IRD and facilitates genetic counseling and disease prediction.
摘要：
遗传性视网膜营养不良(IRD)包括大的慢性异质性遗传疾病。虽然许多致病致病变异与IRD的进展有关，伊朗患者的神经酰胺激酶样(CERKL)基因变异特征不明确.在这项研究中,招募了一个有三代的近亲伊朗家庭，他们的临床诊断为常染色体隐性IRD。通过靶向下一代测序（TGS）和Sanger测序，先证者被发现有一本小说，CERKL基因（NM_001030311.2）的病理纯合缺失变体c.560_568del（p.187_190del）与所有受影响的家庭成员中的疾病共分离。Cerkl在后来的四个视网膜发育阶段高表达，在视网膜变性中起着至关重要的作用。因此,小说的鉴定，IRD家族队列血统中的纯合缺失CERKL变体c.560_568del（p.187_190del）提供了对IRD分子发病机理的见解，并促进了遗传咨询和疾病预测。
