Optical genome mapping of a complex structural rearrangement family line on chromosome 18

Complex chromosomal rearrangement (CCR) refers to a structural rearrangement involving at least two chromosomes or a minimum of three breakpoints. CCR may lead to intellectual disability, structural anomalies, infertility, and recurrent miscarriages. Chromosome karyotyping and chromosomal microarray analysis (CMA) are unable to detect complex chromosomal rearrangements. As multiple diagnostic approaches are available in clinical practice for detecting chromosomal structural abnormalities and copy number variations-each with its own advantages and limitations-selecting the appropriate testing method is crucial for effective clinical management. Optical genome mapping (OGM) is an advanced genomic technology that utilizes ultra-long single-molecule analysis to comprehensively detect chromosomal aberrations and structural variants at high resolution.

Amniocentesis was performed for a 36-year-old multipara (advanced maternal age), with subsequent comprehensive fetal genetic analysis including chromosome karyotyping, CMA, and OGM. Family members underwent peripheral blood karyotyping and OGM.

The fetal karyotype derived from amniotic fluid was 46,XN,?ins(18)(q21.2;p11.31p11.2). CMA demonstrated duplications of four segments and a deletion of one segment on chromosome 18. Therefore, OGM was performed on the fetal and family members to further elucidate the chromosomal structure. The fetus has derived CCRs on chromosome 18 of maternal origin. In contrast, both the mother and the second daughter, who carried the identical CCRs, were phenotypically normal.

OGM is of significant importance in the diagnosis and characterization of CCRs. OGM plays a critical role in diagnosing complex chromosomal rearrangements and has proven to be invaluable in clinical utility.