title: New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma patients: genetic counseling implications.
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.
authors.affiliation: School of Medicine, Institute of Biology and Human Genetics, Belgrade, Serbia and Montenegro.
authors.forename: Milica
authors.initials: M
authors.lastname: Kontic
authors.affiliation: Institute of Biomedical Research "A. Sols", CSIC-UAM, Madrid, Spain.
authors.forename: Iciar
authors.initials: I
authors.lastname: Palacios
authors.affiliation: Institute of Biomedical Research "A. Sols", CSIC-UAM, Madrid, Spain.
authors.forename: Ángelo
authors.initials: Á
authors.lastname: Gámez
authors.affiliation: Institute of Biomedical Research "A. Sols", CSIC-UAM, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Camino
authors.affiliation: Clinical Centre of Serbia, Institute of Ophthalmology, Belgrade, Serbia and Montenegro.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Latkovic
authors.affiliation: Clinical Centre of Serbia, Institute of Ophthalmology, Belgrade, Serbia and Montenegro.
authors.forename: Dejan
authors.initials: D
authors.lastname: Rasic
authors.affiliation: Clinical Centre of Serbia, Institute of Ophthalmology, Belgrade, Serbia and Montenegro.
authors.forename: Vera
authors.initials: V
authors.lastname: Krstic
authors.affiliation: School of Medicine, Institute of Biology and Human Genetics, Belgrade, Serbia and Montenegro.
authors.forename: Vera
authors.initials: V
authors.lastname: Bunjevacki
authors.affiliation: Institute of Biomedical Research "A. Sols", CSIC-UAM, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Alonso
authors.affiliation: Institute of Biomedical Research "A. Sols", CSIC-UAM, Madrid, Spain. apestana@iib.uam.es.|Instituto Investigaciones Biomédicas, C/ Arturo Duperier 4, 28029, Madrid, Spain. apestana@iib.uam.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Pestaña
mesh_terms: D004252:DNA Mutational Analysis; D005817:Genetic Counseling; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D011110:Polymorphism, Genetic; D019572:Retinal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012175:Retinoblastoma / Q000175:diagnosis* / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D015022:Yugoslavia
chemical_list: D016160:Retinoblastoma Protein