Mohd Fadly et al. Journal of Medical Case Reports 2012, 6:30 http://www.jmedicalcasereports.com/content/6/1/30 Page 4 of 7 Figure 2 Profile of the microarray analysis showing the deletion region as indicated in the highlighted area. A dye-swap experiment was performed to maximize the accuracy of detection of the deletion. been reported to be associated with RSTS and is thought to be responsible for the core clinical manifesta- tions of RSTS in our patient. Crebbp (OMIM: 600140) is a transcription coactivator and functions as a potent his- tone acetyltransferase, both of which are essential to normal development [6]. The Crebbp gene is involved in different signaling pathways and in certain cellular func- tions, such as DNA repair, cell growth, differentiation, apoptosis and tumor suppression. Crebbp gene deletion [7] or exon deletion [8] are demonstrated in about 8% to 12% of patients. EP300 (OMIM: 602700) mutations were also identified as another rare cause of RSTS in 3% of patients [6]. The Human Gene Mutation Database (http://www.hgmd.org) holds, at present, 92 different mutations in the Crebbp gene - 13 missense substitu- tions, 20 nonsense substitutions, 10 splicing substitu- tions, 16 small deletions, nine small insertions, two small indels, 19 gross deletions, one gross insertion and two complex rearrangements. Previous studies of patients with RSTS indicated 16 p13.3 deletions of up to 560 kb to 650 kb and including the 5’- and 3’-flanking regions of the Crebbp gene [4,8,9]. Recently, intragenic deletions were detected in two RSTS patients using an exon coverage microarray platform; one in a male patient resulting from deletion of two exons within the Crebbp gene and the other in a female patient resulting from deletion of four exons within the Ep300 gene [10]. Trap1 (OMIM: 606237) is a mitochondrial 90-kilodal- ton heat shock protein (Hsp90). Hsp90 proteins are important and highly conserved molecular chaperones that have key roles in signal transduction, protein fold- ing, protein degradation and morphologic evolution. Hsp90 proteins normally associate with other co-chaper- ones and play important roles in folding newly synthe- sized proteins or stabilizing and refolding denatured proteins after stress. The human Hsp90 family includes 17 genes that fall into four classes. Six genes, Hsp90AA1, Hsp90AA2, Hsp90N, Hsp90AB1, Hsp90B1 and Trap1, were recognized as functional, and the remaining 11 genes were considered putative pseudo- genes [11]. Although Trap1 has not been associated with human disease, the importance of this gene war- rants attention. In addition, a small subset of RSTS cases caused by 16 p13.3 microdeletions involving neighboring genes of Crebbp have recently been sug- gested to be a true contiguous gene syndrome called severe RSTS, or 16 p13.3 deletion syndrome (OMIM: 610543) [12]. Bartsch et al. [12] concluded that