title: Mutational screening of the RB1 gene in Italian patients with retinoblastoma reveals 11 novel mutations.
abstract: Retinoblastoma (RB, OMIM#180200) is the most common intraocular tumour in infancy and early childhood. Constituent mutations in the RB1 gene predispose individuals to RB development. We performed a mutational screening of the RB1 gene in Italian patients affected by RB referred to the Medical Genetics of the University of Siena. In 35 unrelated patients, we identified germline RB1 mutations in 6 out of 9 familial cases (66%) and in 7 out of 26 with no family history of RB (27%). Using the single-strand conformational polymorphism (SSCP) technique, 11 novel mutations were detected, including 3 nonsense, 5 frameshift and 4 splice-site mutations. Only two of these mutations (1 splice site and 1 missense) were previously reported. The mutation spectrum reflects the published literature, encompassing predominately nonsense or frameshift and splicing mutations. RB1 germline mutation was detected in 37% of our cases. Gross rearrangements outside the investigated region, altered DNA methylation, or mutations in non-coding regions, may be the cause of disease in the remainder of the patients. Some cases, e.g. a case of incomplete penetrance, or variable expressivity ranging from retinoma to multiple tumours, are discussed in detail. In addition, a case of pre-conception genetic counselling resolved by rescue of banked cordonal blood of the affected deceased child is described.
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Sampieri
authors.affiliation: Ophtalmological Science and Neuroscience, Siena General Hospital, Siena, Italy.
authors.forename: Theodora
authors.initials: T
authors.lastname: Hadjistilianou
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Speciale
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Mencarelli
authors.affiliation: Surgery Department, University of Siena, Siena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cetta
authors.affiliation: Medical Genetics, Experimental Oncology, Instituto Nazionale Tumori , Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.affiliation: Medical Genetics, Experimental Oncology, Instituto Nazionale Tumori , Milan, Italy.
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.affiliation: Medical Genetics SSD, ASO San Luigi Orbassano, Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giachino
authors.affiliation: Genetics, Biology and Biochemistry Department, University of Torino, Turin, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.affiliation: Pediatrics Department, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Acquaviva
authors.affiliation: Ophtalmological Science and Neuroscience, Siena General Hospital, Siena, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Caporossi
authors.affiliation: University of Siena, Siena, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Frezzotti
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.affiliation: Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy. bruttinim@unisi.it.
authors.forename: Mirella
authors.initials: M
authors.lastname: Bruttini
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D005091:Exons; D005260:Female; D016161:Genes, Retinoblastoma; D005817:Genetic Counseling; D006801:Humans; D007438:Introns; D007558:Italy; D008297:Male; D009154:Mutation; D010375:Pedigree; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D017931:DNA Primers