Combined Optical Genome Mapping and CNV-Seq indentify Complex Y-Chromosome Rearrangements and Ectopy in 46,XX Testicular Disorder of Sex Development
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Objective To clarify the chromosomal structural variations in a patient with 46,XX testicular disorder of sex development (DSD) using combined genetic technologies. Methods Chromosome karyotype analysis and whole exome sequencing (WES) were initially performed in a phenotypically male patient. Further analyses using optical genome mapping (OGM) and CNV-seq were conducted on fresh peripheral blood to characterize structural variations. Result Karyotyping revealed 46,XX,inv(9)(p12q13), and WES suggested possible Y-chromosome sequences. CNV-seq indicated deletions in Xp22.33, Yp11.31-p11.2, and Yp11.2, confirming 46,XX testicular DSD. OGM futher demonstrated a structural translocation Yp segments to the X chromosome short arm, with three breakage-reconnection events in Yp11.2, including deletions and inversions, clarifying the complex Y-chromosome rearrangements and derivative X-chromosome structure. Conclusion Combined OGM and CNV-seq precisely localized Y-chromosome ectopy to the X short arm and characterized its complex rearrangements, providing patients with more accurate and comprehensive genetic diagnosis, and which has important clinical significance for genetic counseling of sex reversal syndrome.
