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. PROCEDURES: 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. (c) 2008 Wiley-Liss, Inc.
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. PROCEDURES: 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. (c) 2008 Wiley-Liss, Inc.
Authors: Zhao Chen; Kimberly Moran; Jennifer Richards-Yutz; Erik Toorens; Daniel Gerhart; Tapan Ganguly; Carol L Shields; Arupa Ganguly Journal: Hum Mutat Date: 2013-12-20 Impact factor: 4.878
Authors: Amal M Mohammed; Alaa K Kamel; Saida A Hammad; Hanan H Afifi; Zeinab El Sanabary; Mostafa Ezz El Din Journal: World J Pediatr Date: 2009-08-20 Impact factor: 2.764
Authors: Junne Kamihara; Franck Bourdeaut; William D Foulkes; Jan J Molenaar; Yaël P Mossé; Akira Nakagawara; Andreu Parareda; Sarah R Scollon; Kami Wolfe Schneider; Alison H Skalet; Lisa J States; Michael F Walsh; Lisa R Diller; Garrett M Brodeur Journal: Clin Cancer Res Date: 2017-07-01 Impact factor: 12.531