title: Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients.
abstract: Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.
authors.affiliation: Oncogenetic Laboratory (OncoLab), Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Alonso
authors.forename: Helena
authors.initials: H
authors.lastname: Frayle
authors.forename: Ibis
authors.initials: I
authors.lastname: Menéndez
authors.forename: Andrés
authors.initials: A
authors.lastname: López
authors.forename: Purificación
authors.initials: P
authors.lastname: García-Miguel
authors.forename: José
authors.initials: J
authors.lastname: Abelairas
authors.forename: Enric
authors.initials: E
authors.lastname: Sarret
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Vendrell
authors.forename: Aurora
authors.initials: A
authors.lastname: Navajas
authors.forename: Mercé
authors.initials: M
authors.lastname: Artigas
authors.forename: José M
authors.initials: JM
authors.lastname: Indiano
authors.forename: Ana
authors.initials: A
authors.lastname: Carbone
authors.forename: Christian
authors.initials: C
authors.lastname: Torrenteras
authors.forename: Itziar
authors.initials: I
authors.lastname: Palacios
authors.forename: Angel
authors.initials: A
authors.lastname: Pestaña
mesh_terms: D003105:Colombia; D003462:Cuba; D004252:DNA Mutational Analysis; D005091:Exons; D016161:Genes, Retinoblastoma; D005838:Genotype; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D013030:Spain
chemical_list: D016160:Retinoblastoma Protein