Tetragametic Chimerism Identified during a Routine Paternity Testing Case

Tetragametic chimerism results when two eggs are fertilized separately by to sperm cells and the resulting embryos are fussed together and developed as a single individual. We reported previously a case of tetragametic chimerism (NEJM 346(20):1545-1552,2002. Another case is widely known ( My Unborn Twin Is The Mother Of My Children: https://www.youtube.com/watch?v=dFf5gKiTGlo).

We identified another case of tetragametic chimerism during routine paternity testing of a trio. The unusual results that we found were: 1) an unexpected XY profile in the mothers’ sample with Amelogenin. 2) two maternal exclusions in FGA and D13S317 and 3) Two apparent paternal exclusions in D13S3158 and CSF1PO.

When the alleged father was analyzed alone with the female child seeking the paternity (analyzed as a duo) with 21 STR, no paternal exclusions were found with a PI 529629 (W=99.999981%).

We interviewed the mother and collected new samples (hair follicles, saliva, buccal swab, menstrual blood, urine fibroblasts) to carry out cytogenetics, mtDNA, Y-STR and X-STR analysis. In addition, another child (male) was also tested with two maternal exclusions found in CSF1PO and D13S317 when blood samples were compared.

A careful review of the STR profile from the mother’s blood sample, showed the presence of additional low intensity peaks in several STR most of them below our threshold for STR analysis.

Cytogenetic analysis in the mother’s sample showed a 46,XY[83],46,XX[17] composition. mtDNA (HV1 and HV2) showed identical sequences between the mother and children.

Y chromosome STR analysis between the mother and male child showed that the Y chromosome in the child was different from the haplotype present in the mother.

Analysis of STR profiles in different samples obtained from the mother, showed in some cases, more than two alleles in several STR markers (Saliva and menstrual blood), and a different STR profile in several markers when compared blood samples with hair, urine fibroblast, and buccal swabs. When the children were compared with the STR profiles found in hair, urine fibroblast, and buccal swabs, the maternal exclusions found initially were resolved.

Our results indicate that tetragametic chimerism, although a rare event, could be more frequent than expected. Tetragametic chimerism should be suspected if unusual Amelogenin findings (both male and female) are found; in maternally exclusion cases; in cases with extra alleles in STR markers; in cases where twin pregnancies (vanishing tween) have been documented; and in infertility treatment where multiple eggs are induced in each menstrual cycle.