48 - Getting to Know Your LCRs: Recognizing and Interpreting Atypical CNVs in Recurrent Syndromic Microdeletion/Duplication Regions Mediated by Alternative Low Copy Repeat Elements

Abstract

Regions of the genome containing multiple low copy repeats (LCRs) are well known for recurrent deletions and duplications. The routine use of array-based technologies has expanded our understanding of the complexity and diversity of these recurrent rearrangements, historically detected by FISH. It is now clear that in addition to the common and clinically well-defined microdeletions/duplications, other CNVs in these regions are mediated by alternative LCRs. Interpretation of these atypical CNVs within regions of syndromic microdeletions/duplications is often challenging, especially when the critical genes for the phenotypes are not well defined. Additionally, identification of relevant patients from the medical literature can be cumbersome, as most historical papers refer to previously established LCR nomenclature rather than genomic coordinates. Additional care must be taken when reporting these results and referencing relevant literature, as there can be significant clinical differences between typical and atypical deletions/duplications. Focusing on genomic regions containing recurrent CNVs mediated by LCRs, we have curated .bed and .aed files to illustrate the position and conventional names of both common and atypical breakpoint LCRs in those regions. This allows for rapid recognition of typical and atypical deletions/duplications, and also provides an easy reference to both LCR nomenclature and current genomic coordinates. We will review the current clinical understanding of both typical and atypical CNVs in recurrent microdeletion/duplication regions (e.g. 22q11.2, 15q11.2-13, and 7q11.23), provide a collection of relevant literature to aid interpretations, and highlight the utility of this easy to use resource when interpreting typical and atypical recurrent LCR-mediated copy number variation.