Characterization of a cryptic 3.3 Mb deletion in a patient with a "balanced t(15;22) translocation" using high...

Patients with an apparently balanced translocation and an abnormal phenotype may carry a cryptic deletion/duplication at their translocation breakpoints that may explain their abnormalities. Using microarray CGH (aCGH) and gene expression arrays we studied a child with t(15;22)(q26.1;q11.2), developmental delay and mild dysmorphic features. A high density aCGH study with 244,000 oligo probes demonstrated a 3.3 Mb deletion immediately adjacent to the 15q breakpoint. Gene expression studies with 44,000 oligos displayed an approximately 50% reduction of the expression of IGF1R gene that was translocated to the der(22). There are 18 known or hypothetical protein coding genes within the deleted region according to UniProt, RefSeq, and GenBank mRNA (UCSC HG17, May 2004). Although two of these genes, RGMA and ST8SIA2, play an important role in neural development, the mild phenotype of our patient indicates that loss of one copy of these genes may not be critical developmentally. The 50% reduction of IGF1R expression could be responsible for the growth deficiency in the patient. Reviewing the few 15q26 microdeletion cases that have been characterized by aCGH, we discovered that deletion of the segment including distal 15q26.2 to the proximal part of 15q26.3 is associated with severe phenotypes. Our experience demonstrates that high-density oligonucleotide-based aCGH is a quick and precise way to identify cryptic copy number changes in "balanced translocations." Expression studies can also add valuable information regarding gene expression changes due to a chromosomal rearrangement. Both approaches can assist in the elucidation of the etiology of unexplained phenotypic differences in cases such as this one.