Hereditary retinoblastoma transmitted by maternal germline mosaicism

Background. Investigating transmission of a constitutive, g78238C>T (R552X), RB1 mutation in four affected children descended from three different unaffected fathers and all Unaffected mother. Procedures. Sequence data analyses and allele-specific PCR assays were used to investigate the presence of the mutation inl four affected children, five (unaffected sibs (or half-sibs), and the unaffected mother. Haplotyping was carried out for confirming that the children descended from different fathers. Results. Haplotyping excluded the possibility of paternal transmission of a de novo mutation and provided evidence of maternal germline mosaicism. The mutation was apparently absent inblood- and buccal cell-DNA of the mother who also showed a normal fundoscopy. Conclusions. Our findings indicated that mosaicism was restricted to the maternal germline. The mutational event Most have occurred at least 4 weeks post-conception, Unlike the early mutational events of most mosaics, occurring between fertilization and the 8th day of conception. The implications of these findings are discussed in view that genetic counselling should discriminate between gerniline mosaicism and de novo events in pseudo-low-penetrant hereditary retinoblastomna.