Novel mutations in the RB1 gene from Chinese families with a history of retinoblastoma
Retinoblastoma is an aggressive eye cancer that develops during infancy and is divided into two clinical types, sporadic and heritable. RB1 has been identified as the only pathological gene responsible for heritable retinoblastoma. Here, we identified 11 RB1 germline mutations in the Han pedigrees of 17 bilateral retinoblastoma patients from China. Four mutations were nonsense mutations, five were splice site mutations, and two resulted in a frame shift due to an insertion or a deletion. Three of the mutations had not been previously reported, and the p.Q344L mutation occurred in two generations of retinoblastoma patients. We investigated phenotypic–genotypic relationships for the novel mutations and showed that these mutations affected the expression, location, and function of the retinoblastoma protein. Abnormal protein localization was observed after transfection of the mutant genes. In addition, changes in the cell cycle distribution and apoptosis rates were observed when the Saos-2 cell line was transfected with plasmids encoding the mutant RB1 genes. Our findings expand the spectrum of known RB1 mutations and will benefit the investigation of RB1 mutation hotspots. Genetic counseling can be offered to families with heritable RB1 mutations.
KeywordsRetinoblastoma RB1 Mutation Genetic counseling
This work was supported by the Scientific Research Program of National Health and Family Planning Commission of China (2014040), the National Natural Science Foundation of China grant (81172323, 81372909), and the Science and Technology Commission of Shanghai (12ZR1417300, 13ZR1423600). We are very grateful to Professor Shanchao Zhao (Southern Medical University, Key Laboratory for Proteomics of Guangdong Province) for providing the wild-type RB1 recombinant plasmid and Professor Yongqiang Hao (Department of Orthopedics, Shanghai Ninth People’s Hospital) for providing the Saos-2 cell line. We wish to acknowledge Wei Liu (Shanghai Institute of Endocrinology, Ruijing Hospital, Shanghai Jiao Tong University School of Medicine) for excellent technical assistance. We are most grateful to the family and the volunteers who participated in this study and to the clinicians and researchers who made this work possible.
Conflicts of interest
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