Novel, Aberrantly Truncated Isoform of Serum CD13 in a Family with High Serum Aminopeptidase N (CD13) Activity

Background: We previously reported a family in which the propositus and both her father and paternal grandmother had high serum aminopeptidase N (CD13; EC 3.4.11.2) activity (autosomal dominant). The molecular mass of the serum CD13 polypeptide of the propositus was larger than that of normal CD13, suggesting either a mutation in the CD13 gene or an abnormality in posttranslational modification of CD13 polypeptide in this family. Methods: Reverse transcription-PCR and direct sequencing were performed with leukocyte CD13 mRNA from the propositus. Two-dimensional electrophoresis and N-terminal amino acid sequencing were performed with serum CD13 from the propositus, the father of the propositus, and healthy volunteers. Results: The sequence of the CD13 cDNA of the propositus was essentially identical with that reported previously. However, the CD13 polypeptide of the propositus and the father of the propositus was truncated, lacking amino acids 1–43 of intact CD13 (43-truncated CD13), whereas CD13 lacking residues 1–58 (58-truncated CD13) and 43-truncated CD13 were detected in serum from healthy volunteers. Conclusions: In serum from healthy volunteers, we found both 58-truncated CD13, a major isoform reported previously, and 43-truncated CD13, a novel, minor isoform with a larger polypeptide. In serum of the family, 43-truncated CD13 was extremely concentrated, suggesting that proteolytic cleavage of CD13 amino acids 43 and 44 (43-truncation) is abnormally promoted. Because no mutation was found in the CD13 cDNA from the propositus, increased serum CD13 in this family seems to be caused by a mutation in a gene that regulates 43-truncation protease activity.