Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients.
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.
Alonso
Javier
J
Oncogenetic Laboratory (OncoLab), Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, Spain.
Frayle
Helena
H
Menéndez
Ibis
I
López
Andrés
A
García-Miguel
Purificación
P
Abelairas
José
J
Sarret
Enric
E
Vendrell
M Teresa
MT
Navajas
Aurora
A
Artigas
Mercé
M
Indiano
José M
JM
Carbone
Ana
A
Torrenteras
Christian
C
Palacios
Itziar
I
Pestaña
Angel
A
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
D016160:Retinoblastoma Protein