摘要
目的分析儿童视网膜母细胞瘤(retinoblastoma,RB)基因突变与临床表型的特点。方法收集2018-2019年重庆医科大学附属第二医院门诊23例(双眼4例,单眼19例)散发性RB患儿,联合全外显子测序以及甲基化测序等方法对其外周血样本进行分子遗传学筛查。结合患儿临床表型及分子遗传学特征进行数据分析。结果23例RB患儿中检测到5例胚系突变,其中3例为RB1基因点突变(c.1333C>T无义突变、c.380G>A错义突变以及c.1940delT移码突变各1例),2例为拷贝数变异(1例RB1基因5~17号外显子杂合缺失以及1例RB1基因及邻近序列约14 Mb片段杂合缺失)。5例基因突变患儿的平均发病年龄为5.4个月,显著早于未突变患儿的发病年龄20.2个月,且基因突变与发病年龄有相关性(r=0.592,P<0.01)。5例基因突变患儿中有3例双眼(3/4)RB,显著高于单眼RB检出率(2/19),累及眼别亦有显著差异(χ~2=8.074,P<0.01)。结论2例新型RB1基因胚系拷贝数变异,补充了RB1基因变异谱;RB1基因胚系突变导致RB患儿易双眼患病,且发病更早。
Objective To analyze the characteristics of gene mutations and clinical phenotypes in children with retinoblastoma.Methods We performed molecular genetic screening in 23 children with sporadic retinoblastoma(bilateral in 4 and unilateral in 19 children)treated in 2018 to 2019 in the Second Affiliated Hospital of Chongqing Medical University by whole exon sequencing and methylation sequencing of the peripheral blood samples.The sequence data were analyzed in relation with the clinical features of the patients to explore the correlation between the genotypes and clinical phenotypes.Results Five pathological germline mutations of RB1 gene were identified in the 23 cases,including 3 cases with point mutations in RB1 gene(nonsense mutation c.1333 C>T,missense mutation c.380 G>A,and frameshift mutation c.1940 delT),1 case with heterozygous deletion of exon 5-17 in RB1 gene and 1 with heterozygous deletion of about 14 Mb fragment of RB1 gene and its adjacent sequence.The patients with genetic mutation had an average onset age of 5.4 months,significantly younger than the others(average onset age of 20.2 months).and a significant correlation was found between gene mutations and the age of disease onset(P<0.01,r=0.592).The detection rate of gene mutations was significantly higher in cases of bilateral tumors than in those with unilateral tumor(3/4 vs 2/19;Chi-square=8.074,P<0.01).Conclusion We identified for the first time 2 new germline copy number variants of RB1 gene in children with retinoblastoma,which expand the spectrum of RB1 gene variations.Germline variation of RB1 gene is associated with a higher likelihood of bilateral eye involvement and an earlier onset of retinoblastoma in children.
作者
李薇薇
刘丹宁
周希瑗
LI Weiwei;LIU Danning;ZHOU Xiyuan(Department of Ophthalmology,the Second Hospital Affiliated of Chongqing Medical University,Chongqing,400010,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2020年第18期1859-1867,共9页
Journal of Third Military Medical University
基金
重庆市社会事业与民生保障科技创新专项重点研发项目(CSTC2017shms-zdyfX0021)
重庆市科卫联合医学科研重点项目(2018ZDXM017)。
