A Transcription Map in the CATCH22 Critical Region: Identification, Mapping, and Ordering of Four Novel Transcripts Expressed in Heart

The acronym CATCH22 is used to indicate collectively a group of related phenotypes, namely velocardiofacial syndrome (VCFS), DiGeorge anomaly (DGA), and conotruncal anomaly face, which are associated with deletions within 22q11.2 in the great majority of patients. A deletion map has allowed us to delimit a smallest region of deletion overlap, considerably smaller than the commonly deleted region. We have mapped within this region the chromosomal breakpoint of a balanced translocation patient presenting with a DGA/VCFS phenotype, making this region the strongest candidate for the location of the gene(s) responsible for the disease phenotype. We report a systematic gene search in this region and show the presence of at least six distinct transcripts, two of which have been previously described. The region searched was approximately 270 kb; therefore, an average of one transcript every 45 kb was found. We generated eight new ESTs and mapped two ESTs present in public databases. All six transcripts are expressed in heart, an organ involved in 70–80% of CATCH22 patients. We show that the multimethod approach to search for expressed sequences is effective and indeed necessary for a comprehensive search and provides molecular tools for further characterization of the potential genes identified.