Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit

Hemizygous deletions on chromosome 22q11.2 result in developmental disorder s referred to as DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS). We report the isolation of a novel gene, PCQAP (PC2 glutamine/Q-rich-associ ated protein), that maps to the DiGeorge typically deleted region and encod es a protein identified as a subunit of the large multiprotein complex PC2, PC2 belongs to the family of the human Mediator complexes, which exhibit c oactivator function in RNA polymerase II transcription. Furthermore, we clo ned the homologous mouse Pcqap cDNA. There is 83% amino acid identity betwe en the human and the mouse predicted protein sequences, with 96% similarity at the amino- and carboxy-terminal ends. To assess the potential involveme nt of PCQAP in DGS/VCFS, its developmental expression pattern was analyzed. In situ hybridization of mouse embryos at different developmental stages r evealed that Pcqap is ubiquitously expressed. However, higher expression wa s detected in the frontonasal region, pharyngeal arches, and Limb buds. Mor eover, analysis of subjects carrying a typical 22q11 deletion revealed that the human PCQAP gene was deleted in all patients. Many of the structures a ffected in: DGS/VCFS evolve from Pcqap-expressing cells. Together with the observed haploinsufficiency of PCQAP in DGS/VCFS patients, this Finding is consistent with a possible role for this novel Mediator subunit in the deve lopment of some of the structures affected in DGS/VCFS. (C) 2001 Academic P ress.