title: [Molecular diagnosis of retinoblastoma: molecular epidemiology and genetic counseling].
abstract: OBJECTIVE
  Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumor in children and a potential cause of blindness from therapeutic eye ablation, second tumors in germ line mutation carriers, and even death when untreated. The molecular scanning of RB1 in search of germ line mutations in 213 retinoblastoma patients from Spain, Cuba, Colombia and Serbia, has led to the detection of 106 mutations whose knowledge is important for genetic counselling and characterization of phenotypic-genotypic relations.
  
  
  METHODS
  Mutational study (PCR-sequentiation and microsatellites analysis) in patients with retinoblastoma, from Spain, Cuba, Colombia and Serbia.
  
  
  RESULTS
  45% of mutations, including most of the frame shift (FS), missense (MS) and splicing (SP), were new, while all nonsense mutations (NS) corresponded to hypermutable sites in RB1. Germ line mutations were found in 22% of unilateral sporadic patients. The incidence of SP plus MS mutations in this group of patients was greater (p = 0.018) than in bilateral patients. The frequency of SP mutations was higher (p = 0.0003) in Spain and France than in Germany and United Kingdom, while the incidence of NS mutations was lower (p = 0.0006). SP mutations were associated with the low penetrance phenotype and were also overrepresented (p = 0.018) in patients with delayed retinoblastoma onset.
  
  
  CONCLUSIONS
  Mutational scanning of unilateral patients is important for genetic counselling and may help decipher the molecular mechanisms leading to low penetrance or expressivity. The functional characterization of mutations associated with low-penetrance or expressivity phenotypes and the molecular classification of tumors using multiple expression profiling is important for a better understanding of the retinoblastoma pathogenesis.
authors.affiliation: OncoLab, Departamento de Biología Molecular y Celular del Cáncer, Instituto de Investigaciones Biomédicas (IIB) Alberto Sols, CSIC-UAM, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Alonso
authors.forename: Itziar
authors.initials: I
authors.lastname: Palacios
authors.forename: Angelo
authors.initials: A
authors.lastname: Gámez
authors.forename: Isabel
authors.initials: I
authors.lastname: Camino
authors.forename: Helena
authors.initials: H
authors.lastname: Frayle
authors.forename: Ibis
authors.initials: I
authors.lastname: Menéndez
authors.forename: Milica
authors.initials: M
authors.lastname: Kontic
authors.forename: Purificación
authors.initials: P
authors.lastname: García-Miguel
authors.forename: Ana
authors.initials: A
authors.lastname: Sastre
authors.forename: José
authors.initials: J
authors.lastname: Abelairas
authors.forename: Enric
authors.initials: E
authors.lastname: Sarret
authors.forename: Constantino
authors.initials: C
authors.lastname: Sabado
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: Jordi
authors.initials: J
authors.lastname: Rosell
authors.forename: Angel
authors.initials: A
authors.lastname: Pestaña
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012175:Retinoblastoma / Q000453:epidemiology* / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D016160:Retinoblastoma Protein