PDF(Pubmed)
Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■这项研究的目的是探索遗传病因，并提出针对视网膜母细胞瘤（RB）和全球发育迟缓（GDD）儿童的遗传诊断和咨询策略。
■我们报告了一个2岁零4个月大的男孩，患有双眼视网膜母细胞瘤和全球发育迟缓（包括智力障碍，语言发展延迟，电机开发延迟，等。).从先证者及其父母分离的外周血单核细胞中提取基因组DNA。对先证者及其父母进行全外显子组测序（WES）以确定遗传病因，随后通过定量聚合酶链反应（qPCR）验证。WES显示RB转录抑制因子1（RB1，OMIM：614041）基因中存在明显的杂合缺失，包括外显子7-8，在受影响的先证者中，但不在他的父母中。此外,确定了两个致病性拷贝数变异（CNV）：分别在7q11.23处的重复和在16p11.2-p12.2处的微缺失。此外，基因组qPCR分析表明，先证者RB1基因中外显子7和外显子8的拷贝数减少了50％，与在他父母身上发现的相比。RB1基因和两种致病性CNV的同时变异可以精确地解释先证者的遗传病因。
■本研究首次报道了在中国患有视网膜母细胞瘤并伴有全球发育迟缓的儿科患者中，RB1基因的新的总体缺失变体与两个致病性CNV共存。此外,我们的发现强烈支持WES在患有RB共病GDD的儿科患者中的使用，建议将WES作为第一层测试。
■我们报告了一个2岁零4个月大的男孩，患有双眼视网膜母细胞瘤和全球发育迟缓（包括智力障碍，语言发展延迟，电机开发延迟，等。).从先证者及其父母分离的外周血单核细胞中提取基因组DNA。对先证者及其父母进行全外显子组测序（WES）以确定遗传病因，随后通过定量聚合酶链反应（qPCR）验证。WES显示RB转录抑制因子1（RB1，OMIM：614041）基因中存在明显的杂合缺失，包括外显子7-8，在受影响的先证者中，但不在他的父母中。此外,确定了两个致病性拷贝数变异（CNV）：分别在7q11.23处的重复和在16p11.2-p12.2处的微缺失。此外，基因组qPCR分析表明，先证者RB1基因中外显子7和外显子8的拷贝数减少了50％，与在他父母身上发现的相比。RB1基因和两种致病性CNV的同时变异可以精确地解释先证者的遗传病因。
■本研究首次报道了在中国患有视网膜母细胞瘤并伴有全球发育迟缓的儿科患者中，RB1基因的新的总体缺失变体与两个致病性CNV共存。此外,我们的发现强烈支持WES在患有RB共病GDD的儿科患者中的使用，建议将WES作为第一层测试。
