Abstract
The purpose of this work was to identify germ line RB1 mutations in 16 Serbian retinoblastoma patients for genetic counselling. Mutation analysis was carried out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1 oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797 del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found in this study. In addition, four intronic variants were observed germ line in some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204-8T/A) are discussed as potential oncogenic mutation candidates. The results show the relevance of studies aimed to investigate the role of intronic variants in exon splicing regulation. Such studies will help to disclose hidden retinoblastoma susceptibilities, important for accurate genetic counselling.
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Abbreviations
- RBDMdb:
-
Retinoblastoma gene mutation database
- WT:
-
Wild-type
- LOH:
-
Loss of heterozygosity
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Acknowledgments
This work was supported by grants from the Comunidad de Madrid (GR/SAL/0855/2004), Ministerio de Educación y Ciencia (SAF2005-00946) and Instituto de Salud Carlos III (PI050128). IP held a postdoctoral contract from the Comunidad de Madrid; AG is a predoctoral fellow from the Ministerio de Educación y Ciencia; IC was contracted with a grant C03/10 from the Instituto de Salud Carlos III; MK held a short term fellowship (ICRETT 1029) from the UICC.
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Kontic, M., Palacios, I., Gámez, Á. et al. New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma patients: genetic counseling implications. J Hum Genet 51, 909–913 (2006). https://doi.org/10.1007/s10038-006-0036-y
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DOI: https://doi.org/10.1007/s10038-006-0036-y
