Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies

“Simple” 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailin g an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations a ssociated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (includingLMNA,USF1,VANGL2,LOR, andPOGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (betweenCPNE9 andBRPF1) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient ’s phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness – rather than lethality issues – may account for the paucity of “ simple” interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the...
Source: Cytogenetic and Genome Research - Category: Genetics & Stem Cells Source Type: research