QUANTIFICATION OF THE PATERNAL ALLELE BIAS FOR NEW GERMLINE MUTATIONSIN THE RETINOBLASTOMA GENE

New germline mutations in the human retinoblastoma gene are known to a rise preferentially on paternally derived chromosomes, but the magnitu de of that bias has not been measured. We evaluated 49 cases with a ne w germline mutation and found that in 40 cases (82%) the mutation aros e on the paternally derived allele. We also evaluated 48 cases likely to have a somatic initial mutation; in this group the initial mutation arose on paternal or maternal chromosomes with approximately equal fr equency. There was no statistically significant difference in the aver age age of fathers of children with new paternal germline mutations fr om the average age of fathers of children with new maternal germline m utations or somatic initial mutations. Combining the data with that fr om previous reports from other groups. the proportion of new germline mutations arising on a paternally derived allele is 85% (based on 72 c ases; 95% confidence interval 76-93%). This number can be useful in th e genetic counseling of some families with retinoblastoma.