Identification of a familial complex chromosomal rearrangement by optical genome mapping

BACKGROUND: Complex chromosomal rearrangements (CCRs) are rare chromosomal structural variations, containing a variety of rearrangements such as translocation, inversion and/or insertion. With the development of cytogenetic and molecular genetic techniques, some chromosomal rearrangements that were initially considered to be simple reciprocal translocations in the past might eventually involve more complex chromosomal rearrangements. CASE PRESENTATION: In this case, a pregnant woman, who had a spontaneous abortion last year, had abnormal prenatal test results again in the second pregnancy. Applying a combination of genetic methods including karyotype analysis, chromosomal microarray analysis, fluorescence in situ hybridization and optical genome mapping confirmed that the pregnant woman was a carrier of a CCR involving three chromosomes and four breakpoints, and the CCR was paternal-origin. Her first and second pregnancy abnormalities were caused by chromosomal microdeletions and microduplications due to the malsegregations of the derivative chromosomes. CONCLUSIONS: We presented a rare familial CCR involving three chromosomes and four breakpoints. This study provided precise and detailed information for the subsequent reproductive decision-making and genetic counselling of the patient.