Pathophysiology

====Velocardiofacial syndrome is a genetic disorder caused by hemizygous microdeletion in chromosome 22q11.2 [5]. The cause of deletion was due to low copy repeats (LCR) during meiotic non-allelic homologous recombination process [3]. About 90% of individuals with VCFS have a 3 Mb deletion with the same breakpoints at each end of the gene [7]. Less than 10% of affected individuals have smaller deletions with similar proximal breakpoint but only 1.5 Mb on the distal breakpoint [7]. There is no reported difference between 3 Mb and 1.5 Mb deletions in its clinical expression. Maybe differences does occur, however, it has not been studied yet due to the large span of the phenotype and the number of deleted genes involved [7].====

====To understand the role of TBX1 gene in human, Christiane Zweier and colleagues (2007) studied 10 patients that has no deletion and with a typical 22q11.2 deletion phenotype. The purpose of their study was to compare the genome of those patients without deletion to those individuals with deletions. They detected in one patient a heterozygous missense mutation in c.582, an evolutionary conserved amino acid histidine was replaced by glutamine at position 194 within the T-box domain (shown in Figure 3A). Figure 3B shows the amino acids sequence alignment of different species in TBX1 with homologues in location 194. Those amino acids with gray background are the conserved amino acids and the light gray background has the similar amino acids. Figure 3C shows the scheme of TBX1C exon 5 where mutation occurred (red arrow) [8].====



====This missense mutation, which may possibly alter the transcriptional process of the TBX1 protein by stabilizing the protein-protein DNA interaction. They concluded that this mutation can result to the same phenotypes expressed with those patients with 22q11.2 deletion syndrome or VCFS. Their experiment provides information about the function of TBX1 in humans and the effect of mutations to the T-box family [8].====