Characterization of a 5.3 Mb deletion in 15q14 by comparative genomic hybridization using a whole genome “tiling path” BAC array in a girl with heart defect, cleft palate, and developmental delay

Abstract

High-resolution array CGH utilizing sets of overlapping BAC and PAC clones ("tiling path") covering the whole genome is a powerful novel tool for fast detection of submicroscopic chromosome deletions or duplications. We describe the successful application of a submegabase resolution whole genome "tiling path" BAC array to confirm and characterize a de novo interstitial deletion of chromosome 15. The deletion has a size of 5.3 Mb and is located within chromosome band 15q14, distal to the Prader-Willi/Angelman region. The affected girl had a heart defect, cleft palate, recurrent infections, and developmental delay. In contrast to GTG banding, array CGH determined the exact number of deleted genes and thus allowed the identification of candidate genes for cleft palate (GREM1, CX36, MEIS2), congenital heart defect (ACTC, GREM1, CX36, MEIS2), and mental retardation (ARHGAP11A, CHRNA7, CHRM5).