SPECTRUM OF SMALL LENGTH GERMLINE MUTATIONS IN THE RB1 GENE

A screening method based on multiplexed automated fragment length anal ysis of polymerase chain reaction products was used to identify germli ne mutations in the RB1 gene. By screening 106 unrelated patients with hereditary retinoblastoma, 20 small deletions (1 -18 bp) and seven in sertions (1-5 bp) were identified, When collating our data with report ed mutations, recurrence of small length mutations was observed at nin e sites within the RB1 gene. Most of these contained monotonic runs or direct-repeats embedded in homocopolymer tracts, While the majority o f mutations resulted in premature truncation, two mutations caused an in-frame loss of F755 and 0540 to E545, respectively. A genotype - phe notype comparison of patients carrying different small length mutation s did not reveal any consistent relation. Particularly, the two patien ts with in-frame mutations showed a high number of tumours consistent with regular-penetrance retinoblastoma.