Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia

Neuroblastoma apoptosis-related RNA-binding protein (NAPOR; HGMW-approved symbol CUGBP2) is a newly discovered gene prominently induced during apoptosis, suggesting that: it plays a role during apoptosis, We have found that it is encoded by a gene located on chromosome 10p13-p14 between Genethon markers D10S547 and D10S223, a region to which we have recently localized a gene responsible for arrhythmogenic right ventricular dysplasia (ARVD). To examine its possible role in the pathogenesis of ARVD, we determined the genomic organization of the human NAPOR gene including its exon-intron boundaries and the putative promoter sequence, which provide a plausible mechanism for its alternative mRNA splicing. We also demonstrated that three isoforms of the NAPOR transcript were differently expressed, with NAPOR-3 being nearly neuron specific while the other two forms were ubiquitously expressed. The expression of NAPOR is differentially regulated during development. Finally, we screened the members of the ARVD family for mutations and identified two DNA sequence variants in the protein-coding exons of NAPOR, neither of which was responsible for ARVD, While the function of NAPOR remains to be elucidated, our current characterization of the NAPOR gene will be valuable for further clinical and functional study, (C) 2001 Academic Press.