Exome and Genome Sequencing to Unravel the Precise Breakpoints of Partial Trisomy 6q and Partial Monosomy 2q

Abstract

Abstract Background Uncovering the precise breakpoints of subchromosomal deletions and duplications could help to clarify the spectrum of the unbalanced translocation and detect the cause of congenital malformations and mental retardation in Children. However, it is challenging to capture the large segment of genomic variants using exome sequencing techniques. Here, we combine exome and genome sequencing techniques to secure the accurate breakpoints of a proband with both heterozygous microduplications in the 6q 25.3-q27region and microdeletions in the 2q37.1-q37.3 region. Case presentation Here, the Whole Exon Sequencing (WES) got clues about the pathological CNVs at chromosomes 2q and 6q but failed to detect the precisely related location. Then we applied the genome sequencing, as copy number variations sequencing (CNV-seq), to compensate for determining the accurate breakpoint sites. These sites could also be ensured by Oxford Nanopore sequencing (ONT) and Optical genome mapping (OGM). The proband showed de novo heterozygous copy number deletion with del(2)(q37.1q37.3)chr2:g.232963568_24305260del and copy number duplication with dup(6)(q25.3q27)chr6:g.158730978_170930050dup which derived from parental balanced translocation t(2;6)(q37.1-37.3;q25.3-27). Different from previous reports about the translocation of 2q and 6q, we get the accurate breakpoint, and the proband showed severe congenital cranial dysinnervation disorders(CCDD), and abnormal thorax development. Conclusions We conclude that it is highly efficient to combine exome and genome sequencing techniques to secure precise breakpoints of subchromosomal deletions and duplications derived from balanced translocation. And the genome sequencing techniques could be CNV-seq, ONT, or OGM.