Forensic analysis of a parthenogenetic 46, XX/46, XY congenital chimera: A case report

Abstract

In forensic identification, chimerism is an extremely rare phenomenon in which DNA samples can easily be misidentified as mixtures from two individuals. If only a single cell population from the chimera is collected, it may lead to false exclusions in paternity testing and errors in forensic conclusions. In China, short tandem repeat analysis is required for victim identification in homicide cases. This study originated from a murder case — the decedent's blood sample exhibited a mixed STR profile suggestive of two contributors. Therefore, 16 additional distinct types of organ tissues from the decedent were collected for comprehensive analysis. Autosomal STR testing revealed that the mixed STR profiles across the 17 different tissues were completely consistent, though the mixture ratios varied among tissues. No more than three alleles were observed at each locus, and the resolved male component M and female component F shared one identical allele at each locus. X-STR profiling showed that all 18 samples displayed no more than two alleles per locus, with consistent typing results. Both A-STR and X-STR findings indicated that components M and F originated from the same maternal chromosome. Copy number variation analysis confirmed the coexistence of two cell lines, 46, XX and 46, XY, in the decedent’s tissues. Cross-validation using multiple methods confirmed that the decedent was an intersex parthenogenetic chimera, with both cell lines randomly participating in tissue and organ differentiation. The resolved component F matched the decedent's son and husband in a parent-child relationship, consistent with a trio kinship. Meanwhile, the male component, together with the female component and the decedent’s sister, was inclined to be considered full siblings based on the combined identity by state score. These results ruled out the possibility that the mixed STR profile resulted from contamination and suggested the presence of normal oocytes in the decedent’s ovarian tissue, indicating that germline cells might not be chimeric. This study provides a deeper exploration of the mechanisms underlying chimerism and offers new insights and references for forensic identification. Future DNA studies of autopsy material may help clarify the incidence, subtypes, and pathogenesis of chimerism, while also determining the optimal tissue types for detecting chimerism and screening for chimerism, thereby supporting related research and practice.