两个Bietti结晶样角膜视网膜营养不良家系的表型及CYP4V2基因变异分析  

Analysis of phenotype and CYP4V2 gene variants in two pedigrees affected with Bietti crystalline corneoretinal dystrophy

作　　者：解燕川 白周现 孙宗立[1] 谷雷[1] 张心愿 孔祥东[2] Xie Yanchuan;Bai Zhouxian;Sun Zongli;Gu Lei;Zhang Xinyuan;Kong Xiangdong(Central Laboratory,the First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan 471003,China;Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450000,China)

机构地区：[1]河南科技大学临床医学院河南科技大学第一附属医院中心实验室,洛阳471003 [2]郑州大学第一附属医院遗传与产前诊断中心,450000

出　　处：《中华医学遗传学杂志》2020年第12期1340-1343,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划 (2018YFC1002203)。

摘　　要：目的对两例Bietti结晶样角膜视网膜营养不良患者的CYP4V2基因进行分析,明确其致病原因,为临床诊断提供依据。方法应用高通量测序法筛查、Sanger测序法验证基因变异位点。利用相关数据库和PubMed文献检索,结合患者临床表现和辅助检查,依据美国医学遗传学与基因组学学会标准与指南判断该基因变异的致病性。结果家系1先证者CYP4V2基因存在c.(802-8)_810delTCATACAGGTCATCGCTinsGC纯合变异,父母未检测;家系2先证者CYP4V2基因存在c.(802-8)_810delTCATACAGGTCATCGCTinsGC和c.958C>T(p.R320X)的复合杂合变异,父母均为变异携带者;两家系的CYP4V2基因的Sanger测序结果与高通量测序一致。CYP4V2基因c.(802-8)_810delTCATACAGGTCATCGCTinsGC变异为剪接变异,剪接变异和无义变异均可产生截短的无功能蛋白产物。依据美国医学遗传学与基因组学学会指南标准此剪接变异及无义变异均为致病性变异(PVS1+PS1+PM2+PM3)。结论CYP4V2基因c.(802-8)_810delTCATACAGGTCATCGCTinsGC纯合变异及c.(802-8)_810delTCATACAGGTCATCGCTinsGC和c.958C>T(p.Arg320X)复合杂合变异分别为这2个家系先证者的致病原因。Objective The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis.Methods The probands were subjected to next generation sequencing(NGS).Suspected variants were verified by Sanger sequencing.Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines.Results A homozygous variant in the CYP4V2 gene c.(802-8)_810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1,parents did not detect;CYP4V2 genes c.(802-8)_810delTCATACAGGTCATCGCTinsGC and c.958 C>T(p.Arg320X)compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers.The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing.The c.(802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant,and both splicing variant and nonsense variant could produce truncated nonfunctional protein products.Based on standards and guidelines by American College of Medical Genetics and Genomics,the CYP4V2 genes c.(802-8)_810del TCATACAGGTCATCGCTinsGC and c.958 C>T(p.Arg320X)were predicted to be pathogenic variants(PVS1+PS1+PM2+PM3).Conclusion The homozygous variant c.(802-8)_810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c.(802-8)_810delTCATACAGGTCATCGCTinsGC and c.958C>T(p.Arg320X)in CYP4V2 gene are the cause of the disease in the probands of two pedigrees,respectively.

关 键 词：Bietti结晶样角膜视网膜营养不良 CYP4V2基因 剪接变异 无义变异 

分 类 号：R774.1[医药卫生—眼科]