Impact of RB1 gene mutation type in retinoblastoma patients on clinical presentation and management outcome.

OBJECTIVE/BACKGROUND: Retinoblastoma (RB), the most common intraocular malignancy in children, is caused by biallelic inactivation of the human retinoblastoma susceptibility gene (RB1). We are evaluating the impact of the type of RB1 gene mutation on clinical presentation and management outcome. METHODS: A retrospective case series of 50 patients with RB. Main outcomes were clinical and pathologic features and types of RB1 gene mutations detected using quantitative multiplex polymerase chain reaction (PCR), allele-specific PCR, next-generation sequencing analysis, and Sanger sequencing. RESULTS: Twenty (40%) patients had unilateral RB and 30 (60%) had bilateral RB. Overall, 36 (72%) patients had germline disease, 17 (47%) of whom inherited the disease. Of these 17 inherited cases, paternal origin of the RB1 mutation was seen in 15 (88%). The overall eye salvage rate was 74% (n = 49/66; 100% for Groups A + B + C, and 79% for Group D eyes). The most frequent type of mutation was a nonsense mutation generating a stop codon (15/36, 42%). Other mutations that result in a premature stop codon due to deletions or insertions with donor splice site or receptor splice site mutations were detected in 7/36 (19%), 10/36 (28%), and 2/26 (6%) patients, respectively. The remaining two (6%) patients had frameshift mutation. Patients with deletion, acceptor splice site, and frameshift mutations presented with more advanced ICRB (International Classification of Retinoblastoma) stage (75% diagnosed with Group D or E), even though there was no significant difference in eye salvage rate or tumor invasiveness between patients with different types of mutations. CONCLUSION: Despite the heterogeneous nature of RB1 gene mutations, tumor stage remains the most important predictive factor for clinical presentation and outcome. Furthermore, acceptor splice site and frameshift mutations are associated with more advanced tumor stage at diagnosis.

Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan.

Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.

Safenectomía endoscópica en pacientes con insuficiencia de safena magna / Endoscopic saphenectomy in patients with saphena magna's insufficiency

Entre marzo de 1999 y octubre de 2001 en la unidad de Cirugía Endoscópica del Servicio de Cirugía II en el Hospital Universitario de Caracas, se realizó un estudio con el objetivo primordial de describir la técnica quirúrgica para safenectomía endoscópica en pacientes con insuficiencia de safena magna. Se evaluó además, el tiempo operatorio, las complicaciones posoperatorias y la conformidad del paciente con la técnica realizada, comparando el uso de anestesia troncular versus epidural. El promedio de tiempo quirúrgico fue de 62,5 minutos para el grupo A y de 87 para el B. El 83 por ciento de los pacientes tuvo un dolor posoperatorio clasificado como bajo en el grupo A y 90 por ciento en el B. Se convirtió un paciente a cirugía abierta (5,88 por ciento). Hubo dos casos de linforragia (12,5 por ciento) ambos en el grupo A y obesos y tres equimosis (uno distal en el A y dos proximales en el B), no hubo infecciones y el 90 por ciento de los pacientes se mostraron conformes con el procedimiento. La safenectomía endoscópica con anestesia troncular es un excelente procedimiento para el tratamiento quirúrgico de los pacientes con insuficiencia de safena magna seleccionados, bien tolerada y con bajo índice de complicaciones