Analysis of aberrantly spliced HRPT2 transcripts and the resulting proteins in HPT-JT syndrome

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The risk for parathyroid carcinoma is high in those with the HPT-JT syndrome. Parafibromin is a protein derived from HRPT2 gene and its inactivation has been coupled to familial form of parathyroid malignancy. We previously identified altered transcripts resulting from splice site mutation of the HRPT2 gene in a family with this syndrome. In the present work, we investigated the stability of the altered HRPT2 transcripts and translation products produced in the HPT-JT syndrome. We quantified the differentially expressed HRPT2 mRNAs using real-time RT-PCR and developed a novel monoclonal parafibromin antibody to study the expression of parafibromin in the HPT-JT syndrome. The relative quantification ratios of the wild type HRPT2 mRNA, 23 bp deleted HRPT2 mRNA, and 70 bp deleted HRPT2 mRNA in the HPT-JT syndrome were 0.68, 0.17 and 0.15, respectively. But endogenous parafibromin expression was not detectable in the HPT-JT syndrome carcinoma. The altered HRPT2 mRNAs resulting from the splice site mutation in the HPT-JT syndrome were stable, but their parafibromin translation products from the HPT-JT syndrome carcinoma were probably degraded rapidly. Additional studies that aim to fully characterize the consequences of altered HRPT2 mRNAs in HPT-JT syndrome are required to explore these possibilities.