儿童视网膜母细胞瘤的基因型及临床表型分析

李薇薇; 刘丹宁; 周希瑗

doi:10.16016/j.1000-5404.202003399

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儿童视网膜母细胞瘤的基因型及临床表型分析

临床医学 | 更新时间：2026-01-09

- 儿童视网膜母细胞瘤的基因型及临床表型分析
- Analysis of gene mutations and clinical phenotypes in children with retinoblastoma
- 第三军医大学学报 2020年42卷第18期页码：1859-1867
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院眼科
- 作者简介：
  
  [ 周希瑗，E-mail: zhouxiyuan2002@aliyun.com ZHOU Xiyuan, E-mail: zhouxiyuan2002@aliyun.com
- 基金信息：
  
  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)
- DOI：10.16016/j.1000-5404.202003399
  中图分类号： R394.3;R730.23;R739.72
- 收稿：2020-03-31，
  
  修回：2020-06-22，
  
  纸质出版：2020-09-30
- 稿件说明：
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李薇薇, 刘丹宁, 周希瑗. 儿童视网膜母细胞瘤的基因型及临床表型分析[J]. 第三军医大学学报, 2020,42(18):1859-1867.

Weiwei LI, Danning LIU, Xiyuan ZHOU. Analysis of gene mutations and clinical phenotypes in children with retinoblastoma[J]. Journal of Third Military Medical University, 2020, 42(18): 1859-1867.
李薇薇, 刘丹宁, 周希瑗. 儿童视网膜母细胞瘤的基因型及临床表型分析[J]. 第三军医大学学报, 2020,42(18):1859-1867. DOI： 10.16016/j.1000-5404.202003399.

Weiwei LI, Danning LIU, Xiyuan ZHOU. Analysis of gene mutations and clinical phenotypes in children with retinoblastoma[J]. Journal of Third Military Medical University, 2020, 42(18): 1859-1867. DOI： 10.16016/j.1000-5404.202003399.

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(

=0.592，

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

=8.074，

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。

Abstract

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.1333C

missense mutation c.380G

and frameshift mutation c.1940delT)

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 (

0.01

=0.592). The detection rate of gene mutations was significantly higher in cases of bilateral tumors than in those with unilateral tumor (3/4

2/19;

Chi

-square=8.074

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.

关键词

Keywords

references

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