{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:37:16Z","timestamp":1780526236099,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Retinoblastoma (Rb) is a rare intraocular malignancy that originates in the retina of children under 5\u2009years of age. Approximately one\u2010third of children diagnosed with retinoblastoma are associated with germline mutations in one of the\n                      <jats:italic>RB1<\/jats:italic>\n                      alleles. In this study, we aim to identify\n                      <jats:italic>RB1<\/jats:italic>\n                      mutations in retinoblastoma patients using Sanger sequencing in combination with multiplex ligation\u2010dependent probe amplification (MLPA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      The genomic DNA of 167 Rb patients was isolated from peripheral blood and their clinical information was extracted from medical records. The mutations in the\n                      <jats:italic>RB1<\/jats:italic>\n                      gene were identified through PCR sequencing. Negative results from the PCR sequencing were further analyzed using MLPA reactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RB1<\/jats:italic>\n                      mutations were identified in 56 of the 167 (33.5%) patients. The common mutation types were frameshift mutations (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919), followed by nonsense (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920), splicing (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098), missense (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095), and whole exon deletion (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092). The overall survival rate was 98.2%, with an average follow\u2010up duration of 59\u2009months. Moreover, germline\n                      <jats:italic>RB1<\/jats:italic>\n                      mutation's correlation with enucleation rates is less pronounced in unilateral cases (12.1%) compared to bilateral cases (65.5%). A total of 13 novel mutations have been identified, of which four are specifically associated with enucleation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides a comprehensive analysis of\n                      <jats:italic>RB1<\/jats:italic>\n                      germline mutations in a group of cases with Rb, leading to the identification of 13 novel mutations in Rb patients at a referral center in Iran. We expect that our findings will yield valuable insights to inform the management and genetic counseling of Rb patients, as well as their relatives who are at a higher risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70922","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:55:02Z","timestamp":1746176102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Delving Into Retinoblastoma Genetics: Discovery of Novel Mutations and Their Clinical Impact: Retrospective Cohort Study"],"prefix":"10.1002","volume":"14","author":[{"given":"Mohammad","family":"Faranoush","sequence":"first","affiliation":[{"name":"Pediatric Growth and Development Research Center Institute of Endocrinology and Metabolism, Iran University of Medical Sciences  Tehran 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