Abstract
A chimera is an organism whose DNA is derived from multiple zygotes whereas a mosaic individual’s DNA is entirely derived from a single zygote. We report a case of a chimera who also had cytogenetic features of mosaicism. A 39-year old father of one child, healthy, morphologically normal Korean male with apparent B3 blood group was identified at the time of blood donation. On forward typing 50% of his RBCs were strongly agglutinated by monoclonal anti-B in the manual tube method. The remaining RBCs were type O. Reverse typing revealed a strong anti-A. Complete ABO exon and flanking intronic region sequencing unexpectedly revealed an O01/O02 genotype. He had never been transfused nor received a BMT, and denied having a twin. Chimerism or mosaicism was suspected so additional specimens were collected from the propositus and his parents. Extended RBC phenotyping of the propositus by the gel card technique using monoclonal reagents revealed mixed field agglutination in the M, Kpb, Lub and Jka antigens. B allele haplotype-specific PCR, and exon 6 and 7 cloning and sequencing performed on genomic DNA from the propositus revealed a third ABO allele, B101. Sequencing of exons 6 and 7 and flanking intronic regions of his parents’ ABO alleles revealed a B101 allele in both parents along with an O01 allele (maternal) and an O02 allele (paternal). A total of 9 STR loci were analyzed on DNA extracted from blood, buccal swabs and hair from the propositus and on DNA isolated from peripheral blood lymphocytes from both his parents. Four loci demonstrated a pattern consistent with a double paternal DNA contribution, thus confirming the presence of chimerism (Table 1). Sequence-based typing of HLA class I and II loci was performed on DNA from peripheral blood lymphocytes from these 3 family members but revealed only a single allelic contribution from both parents in the propositus. The propositus’ karyotype revealed a mosaic pattern with 32/50 metaphases demonstrating 46, XY and 18/50 metaphases demonstrating 47, XYY. Overall, an extra paternal set of DNA markers was demonstrable by STR analysis in tissues arising from different germ layers. The propositus is thus a dispermic chimera most likely resulting from parthenogenetic division of the ovum and its subsequent fertilization by two spermatozoa: one with a 23, Y DNA complement and the second with a different 24, YY complement. This would explain the apparent single maternal DNA contribution. Alternatively a non-dysjunction event producing the mosaic 47, XYY karyotype could have occurred after fertilization. Given the mixed field blood group his ABO genotype is most likely B101/O01 and O01/O02. Consistent with other cases of mosaic 47, XYY syndrome our propositus is healthy, morphologically normal and fertile. This is the first case of a dispermic chimera with mosaic 47, XYY syndrome detected at the time of blood donation.
STR results demonstrating a double paternal DNA contribution in disparate tissues DNA polymorphism Father Mother Propositus (blood) Propositus (buccal swab) Propositus (hair) D3S1358 15,16 16,17 15,16,17 15,16,17 15,16,17 D5S818 10,12 9,13 10,12,13 10,12,13 10,12,13 D13S317 12,14 8,9 9,12,14 9,12,14 9,12,14 D18S51 16,19 14,15 15,16,19 15,16,19 15,16,19
Cytogenetic analysis of peripheral blood lymphocytes of children treated with nitrofurantoin for recurrent urinary tract infection
