■视网膜母细胞瘤,一种起源于视网膜的儿童癌症,主要归因于致病性RB1突变本研究的目的是在约旦人群中的个体中进行单侧视网膜母细胞瘤病例中的RB1基因的突变分析。
■在这项研究中,收集50例单侧Rb患者的外周血,提取基因组DNA,并且使用下一代测序(NGS)分析鉴定突变。
■在这个由50名单侧Rb无关患者组成的队列中,诊断时的中位年龄为8个月(平均值,12个月;范围;2周至54个月)。28人(56%)是男性,29人(58%)患有右眼疾病,3(6%)有Rb阳性家族史,20(40%)在生命的第一年内被诊断出。50例患者中有14例(28%)检测到RB1基因致病突变,表明种系疾病。在单方面非家族性病例中,发现47个中的11个(23%)具有种系RB1突变。总的来说,5(36%)种系病例在父母一方检测到与遗传性疾病一致的相同突变(4(80%)是父系起源的);其中3(60%)影响了携带者父母,2人(40%)的父母未受影响.9名(64%)患者有无义突变,和6(43%)有马赛克突变。基因检测阳性的重要预后因素是阳性家族史(p=0.018)和诊断年龄小于12个月(p=0.03)。中位随访54个月,2例(4%)患者死于远处转移。全眼抢救率为44%(n=22/50)眼;A组100%,B,C,D组60%,E组眼睛没有。种系突变的存在与眼部挽救的结果之间没有相关性,转移,和生存。
■在这项研究中,28%的单侧Rb患者存在种系RB1突变,其中43%是遗传的,三分之一出现在他们生命的第一年之后。因此,分子筛查对于在单侧病例中遗传Rb风险的遗传咨询至关重要,包括那些没有家族史的人,无论诊断时的年龄。然而,种系突变似乎不能显著预测患者眼部挽救的预后,转移,和生存。
UNASSIGNED: Retinoblastoma, a childhood cancer originating in the retina, is primarily attributed to pathogenic RB1 mutations The aim of this study is to conduct a mutational analysis of the RB1 gene in cases of
unilateral Retinoblastoma among individuals within the Jordanian population.
UNASSIGNED: In this study, the peripheral blood of 50
unilateral Rb patients was collected, genomic DNA was extracted, and mutations were identified using Next Generation Sequencing (NGS) analysis.
UNASSIGNED: In this cohort of 50 unrelated patients with
unilateral Rb, the median age at diagnosis was eight months (mean, 12 months; range; 2 weeks to 54 months). Twenty-eight (56%) were males, 29 (58%) had the disease in the right eye, 3 (6%) had a positive family history of Rb, and 20 (40%) were diagnosed within the first year of life. RB1 gene pathogenic mutations were detected in 14 out of 50 (28%) patients, indicating germline disease. Among
unilateral non-familial cases, 11 out of 47 (23%) were found to have germline RB1 mutations. Overall, five (36%) of the germline cases had the same mutation detected in one of the parents consistent with an inherited disease (four (80%) were of paternal origin); 3 (60%) of these had affected carrier parent, two (40%) had an unaffected carrier parent. Nine (64%) patients had the nonsense mutation, and six (43%) had the mosaic mutation. The significant prognostic factors for positive genetic testing were positive family history (p = 0.018) and age at diagnosis less than 12 months (p = 0.03). At a median of 54 months follow-up, two (4%) patients were dead from distant metastasis. The overall eye salvage rate was 44% (n = 22/50) eyes; 100% for groups A, B, and C, 60% for group D, and none for group E eyes. There was no correlation between the presence of germline mutation and outcome in terms of eye salvage, metastasis, and survival.
UNASSIGNED: In this study, 28% of patients with
unilateral Rb had germline RB1 mutations, of which 43% were inherited, and one-third presented beyond their first year of life. Therefore, molecular screening is critical for genetic counseling regarding the risk for inherited Rb in unilateral cases, including those with no family history, regardless of the age at diagnosis. However, germline mutations did not appear to significantly predict patient outcomes regarding eye salvage, metastasis, and survival.