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 an unaffected mother.


METHODS
Sequence data analyses and allele-specific PCR assays were used to investigate the presence of the mutation in 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 in blood- 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 must 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 germline mosaicism and de novo events in pseudo-low-penetrant hereditary retinoblastoma.
Barbosa
Raquel H
RH
Genetics Division, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Vargas
Fernando R
FR
Aguiar
Fernanda C C
FC
Ferman
Sima
S
Lucena
Evandro
E
Bonvicino
Cibele R
CR
Seuánez
Héctor N
HN
D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D016161:Genes, Retinoblastoma; D005817:Genetic Counseling; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*
D016160:Retinoblastoma Protein