title: Novel mutations in the RB1 gene from Chinese families with a history of retinoblastoma.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhi Zao Ju Road, Shanghai, 200011, People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.forename: Junyang
authors.initials: J
authors.lastname: Zhao
authors.forename: Jiayan
authors.initials: J
authors.lastname: Fan
authors.forename: YiXiong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Huaidong
authors.initials: H
authors.lastname: Song
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D044466:Asian People; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002681:China; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D016160:Retinoblastoma Protein