%0 Journal Article
%T Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization.
%A Xiao Y
%A Cheng D
%A Luo K
%A Li M
%A Tan Y
%A Lin G
%A Hu L
%J J Assist Reprod Genet
%V 41
%N 1
%D 2024 Jan 23
%M 37993578
%F 3.357
%R 10.1007/s10815-023-02986-7
%X <B>OBJECTIVE: </B>To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples.<BR><B>METHODS: </B>MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers.<BR><B>RESULTS: </B>In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences.<BR><B>CONCLUSIONS: </B>Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.