Genomic disorders contribute significantly to genetic disease and, as detection 
methods improve, greater numbers are being defined. Paralogous low copy repeats 
(LCRs) mediate many of the chromosomal rearrangements that underlie these 
disorders, predisposing chromosomes to recombination errors. Deletions of 
proximal 22q11.2 comprise the most frequently occurring microdeletion syndrome, 
DiGeorge/Velocardiofacial syndrome (DGS/VCFS), in which most breakpoints have 
been localized to a 3 Mb region containing four large LCRs. Immediately distal 
to this region, there are another four related but smaller LCRs that have not 
been characterized extensively. We used paralog-specific primers and long-range 
PCR to clone, sequence, and examine the distal deletion breakpoints from two 
patients with de novo deletions mapping to these distal LCRs. Our results 
present definitive evidence of the direct involvement of LCRs in 22q11 deletions 
and map both breakpoints to the BCRL module, common to most 22q11 LCRs, 
suggesting a potential region for LCR-mediated rearrangement both in the distal 
LCRs and in the DGS interval. These are the first reported cases of distal 22q11 
deletions in which breakpoints have been characterized at the nucleotide level 
within LCRs, confirming that distal 22q11 LCRs can and do mediate rearrangements 
leading to genomic disorders.