The molecular mechanisms of recombinant chromosome 18 with parental pericentric inversions and a review of the literature

Chromosomal rearrangements mostly result from non-allelic homologous recombination mediated by low-copy repeats (LCRs) or segmental duplications (SDs). Recent studies on recombinant chromosome 18 (rec (18)) have focused on diagnoses and clinical phenotypes. We diagnosed two cases of prenatal rec (18) and identified precise breakpoint intervals using karyotype and chromosomal microarray analyses. We analyzed the distribution characteristics of breakpoint repetitive elements to infer rearrangement mechanisms and reviewed relevant literature to identify genetic trends. Among the 12 families with 25 pregnancies analyzed, 68% rec (18), 24% spontaneous abortions, and 8% normal births were reported. In the 17 rec (18) cases, 65% presented maternal origin and 35% were paternal. Short-arm breakpoints at p11.31 were reported in 10 cases, whereas the long-arm breakpoints were located at q21.3 (6 cases) and q12 (4 cases). Breakpoints of pericentric inversions on chromosome 18 are concentrated in p11.31, q21.3, and q12 regions. Rearrangements at 18p11.31 are non-recurrent events. ALUs, LINE1s, and MIRs were enriched at the breakpoint regions (1.85 to 3.42-fold enrichment over the entire chromosome 18), while SDs and LCRs were absent. ALU subfamilies had sequence identities of 85.94% and 83.01% between two pair breakpoints. Small repetitive elements may mediate recombination-coupled DNA repair processes, facilitating rearrangements on chromosome 18. Maternal inversion carriers are more prone to abnormal recombination in prenatal families with rec (18). Recombinant chromosomes may present preferential segregation during gamete formation.