Case report: Genetic diagnoses in a pediatric patient with retinoblastoma and comorbid global developmental delay: three distinct entities diagnosed by whole exome sequencing in a single patient

Jing Chen; Shuo Yang; He Wang; Hongjing Wang; Yuanyuan Xiao; Shanling Liu

doi:10.3389/fnins.2024.1391596

Case report: Genetic diagnoses in a pediatric patient with retinoblastoma and comorbid global developmental delay: three distinct entities diagnosed by whole exome sequencing in a single patient

Front Neurosci. 2024 Jul 23:18:1391596. doi: 10.3389/fnins.2024.1391596. eCollection 2024.

Authors

Jing Chen^{1

2}, Shuo Yang^{1

2}, He Wang^{1

2}, Hongjing Wang^{2

3}, Yuanyuan Xiao^#^{1

2}, Shanling Liu^#^{1

2}

Affiliations

¹ Department of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
² Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, China.
³ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD).

Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband.

Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.

Keywords: RB1; case report; global developmental delay; retinoblastoma; whole exome sequencing.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Key Research and Development Program of China (2022YFC2703300 and 2022YFC2703302).