title: A deep intronic mutation in the RB1 gene leads to intronic sequence exonisation.
abstract: Familial forms of retinoblastoma, an embryonic neoplasm of retinal origin, are caused by constitutional mutations of the RB1 gene. In this paper, we describe a family with retinoblastoma affecting two brothers with no previous family history of cancer. Complete RB1 mutational screening including point mutation and large rearrangement screening failed to demonstrate any mutation. The whole coding sequence was therefore investigated at the cDNA level, demonstrating a 103 bp intronic insertion between exons 23 and 24, leading to subsequent frameshift and premature termination of translation. This intronic exonisation was caused by a deep intronic mutation in intron 23 generating a cryptic 3' splice site. This is the first report of a deep intronic mutation in RB1 and is a proof of concept that some undetected RB1 mutations should be investigated at the cDNA level, particularly in hereditary forms of retinoblastoma.
authors.affiliation: Service de Génétique Oncologique, Institut Curie, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dehainault
authors.forename: Dorothée
authors.initials: D
authors.lastname: Michaux
authors.forename: Sabine
authors.initials: S
authors.lastname: Pagès-Berhouet
authors.forename: Virginie
authors.initials: V
authors.lastname: Caux-Moncoutier
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Philippe
authors.initials: P
authors.lastname: Parent
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: Claude
authors.initials: C
authors.lastname: Houdayer
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D016161:Genes, Retinoblastoma; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing; D019572:Retinal Neoplasms / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D022821:RNA Splice Sites; D016160:Retinoblastoma Protein