Germline Deletions in RB1 Gene and in 13q14 Chromosomal Region in Retinoblastoma - Abstract
Carriers of germline constitutional pathogenic mutations tend to develop bilateral retinoblastoma. Among carriers of germline mutations in RB1 gene, about 14% of the
probands carry gene or chromosomal deletions that include partial or complete loss of one allele of RB1 gene. We have used MLPA technique to search for germline deletions
in RB1 and in five adjacent genes (SUCLA2, MED4, ITM2B, RCBTB2, and DLEU1), in 13q14 chromosomal region in 9 carriers of retinoblastoma without germline point mutation
in RB1. The deletions were confirmed by array-CGH and quantitative relative real-time PCR techniques. Partial RB1 deletions were found in four probands, and five probands
carried complete RB1 deletion that varied in size from 12 to 42 Mb. All four cases with at least one breakpoint within RB1 gene developed bilateral disease. Among five carriers
of complete RB1 deletion, two were unilateral. In order to investigate the hypothesis that complete RB1 deletions are associated with incomplete penetrance, we have identified 14
studies where germline RB1 deletions could be correlated with disease laterality. Fisher’s test showed that carriers of partial RB1 deletion more probably develop bilateral/trilateral
disease, whereas carriers of complete RB1 deletions have a higher probability of incomplete penetrance (unilateral disease) (p=0.000017). In addition, is demonstrated difference
statistically significant for partial deletions that affect female patients.