Identification of 46,XX/46,XY chimerism in a normal fertile male by low-pass copy number variation sequencing and NGS-based STR tests.

To describe a rare case of a normal fertile male with the specific tissue distribution of 46,XX in the peripheral blood and gonadal chimerism confirmed by the novel next-generation sequencing (NGS) methodology. Cytogenetic analyses, low-pass copy number variation sequencing (CNV-seq) and NGS-based short tandem repeat (STR) tests. Routine peripheral blood karyotyping showed 46,XX. Fluorescence in situ hybridization (FISH) analysis of lymphocyte metaphase nuclei confirmed 46,XX and sex-determine region Y (SRY)-negative. Further CNV-seq revealed the presence of Y chromosome in the semen. NGS-based STR tests discovered low-level Y chromosome in the buccal mucosa and three alleles in the semen, suggesting that this chimerism is likely the outcome of a parthenogenetically activated oocyte fertilized by a Y and X sperm. The patient underwent intracytoplasmic sperm injection (ICSI) and resulted in a normal singleton pregnancy. Individuals with 46,XX/46,XY chimerism in the gonad can display normal phenotype and fertility. NGS has proved to be a promising alternative to conventional chimerism assays.