Mutational screening of the RB1 gene in Italian patients with retinoblastoma reveals 11 novel mutations.
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.
Sampieri
Katia
K
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
Hadjistilianou
Theodora
T
Ophtalmological Science and Neuroscience, Siena General Hospital, Siena, Italy.
Mari
Francesca
F
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
Speciale
Caterina
C
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
Mencarelli
Maria Antonietta
MA
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
Cetta
Francesco
F
Surgery Department, University of Siena, Siena, Italy.
Manoukian
Siranoush
S
Medical Genetics, Experimental Oncology, Instituto Nazionale Tumori , Milan, Italy.
Peissel
Bernard
B
Medical Genetics, Experimental Oncology, Instituto Nazionale Tumori , Milan, Italy.
Giachino
Daniela
D
Medical Genetics SSD, ASO San Luigi Orbassano, Turin, Italy.
Pasini
Barbara
B
Genetics, Biology and Biochemistry Department, University of Torino, Turin, Italy.
Acquaviva
Antonio
A
Pediatrics Department, University of Siena, Siena, Italy.
Caporossi
Aldo
A
Ophtalmological Science and Neuroscience, Siena General Hospital, Siena, Italy.
Frezzotti
Renato
R
University of Siena, Siena, Italy.
Renieri
Alessandra
A
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
Bruttini
Mirella
M
Medical Genetics, Molecular Biology Department, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy. bruttinim@unisi.it.
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*
D017931:DNA Primers