P-719 Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization

Abstract Study question What are breakpoint characteristics of ABCR carriers? the genetic risks carriers caused by chromosome rearrangements? Summary answer We analyzed ABCR's breakpoints and found that heterogeneous deletion some AD disease-related genes may not result in clinical phenotype. is known already ABCRs common chromosomal abnormalities. People with generally lack any visible abnormal features; however, during childbirth, pairing missegregation homologous chromosomes can lead to production unbalanced gametes, resulting spontaneous abortion or birth children disorders. Prenatal diagnosis preimplantation effectively prevent rearrangements, but no substantial data has been collected report on potential breakage rearrangement. design, size, duration This a retrospective study 2441 1219 who underwent Preimplantation Genetic Testing (PGT) at Reproductive Hospital Citic-Xiangya from August 1, 2016 December 31, 2021. Participants/materials, setting, methods All patients this sought PGT treatment due primary secondary infertility ABCRs. To characterize breakpoints, MicroSeq technique, which involves microdissection next generation sequencing, was employed. Additionally, gap-junction PCR Sanger sequencing were utilized further validate breakpoints. Main results role chance In study, we retrospectively rearrangement localization carriers, including 2364 regions 1182 reciprocal translocations, 68 34 inversions, 9 3 insertional translocations. only identified 8q24.13, 11q11.23, 22q11.21 as previously reported hotspots balanced breaks, also 10 Mb region 12q24.13-q24.3 possible rare breaks. average range technology within 3.8 Kb, clarified 95.82% (2339/2441) rearrangements whether they broke not. 960 interrupted, 53 autosomal dominant mode inheritance (AD) interrupted. Clinical phenotypic evaluation these carrying interrupted interruptions have Limitations, reasons for caution cannot precisely pinpoint gene single base level. Moreover, comprehensively assessed other characteristics, alteration function Haploinsufficiency could be confirmed. position effect evaluated. Wider implications findings investigation offers reference evaluating pathogenicity protein-truncation mutations genes. Trial registration number Not applicable