Analysis of gene mutations and clinical phenotypes in children with retinoblastoma

Weiwei LI; Danning LIU; Xiyuan ZHOU

doi:10.16016/j.1000-5404.202003399

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Analysis of gene mutations and clinical phenotypes in children with retinoblastoma

Clinical Medicine | 更新时间：2026-01-09

- Analysis of gene mutations and clinical phenotypes in children with retinoblastoma
- Journal of Third Military Medical University Vol. 42, Issue 18, Pages: 1859-1867(2020)
- 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：
- 基金信息：
  
  the Key Sci-tech Innovation Project for Social Undertakings and People's Livelihood in Chongqing(CSTC2017shms-zdyfX0021);the Joint Key Medical Research Project of Chongqing Municipal Science and Technology and Health Commissions(2018ZDXM017)
- DOI：10.16016/j.1000-5404.202003399
  CLC： R394.3;R730.23;R739.72
- Received：31 March 2020，
  
  Revised：2020-06-22，
  
  Published：30 September 2020
- 稿件说明：
移动端阅览
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：

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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