Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene

Marked hypertriglyceridemia resulting from impaired activation of lipoprotein lipase. in most cases of apoc-ii deficiency,causative mutations have been found in the protein-coding region of apoc2; however,several atypical cases of apoc-ii deficiency were reported to have markedly reduced,but detectable levels of plasma apoc-ii protein (hereafter referred to as hypoapoc-ii),which resulted from decreased promoter activity or improper splicing of apoc-ii mrna due to homozygous mutations in apoc2. here we aim to dissect the molecular bases of a new case of hypoapoc-ii. methods: we performed detailed biochemical/genetic analyses of our new case of hypoapoc-ii,manifesting severe hypertriglyceridemia (plasma triglycerides,3235 mg·dl-1) with markedly reduced levels of plasma apoc-ii (0.6 mg·dl-1). results: we took advantage of a monocyte/macrophage culture system to prove that transcription of apoc-ii mrna was decreased in the patient's cells,which is compatible with the reported features of hypoapoc-ii. concomitantly,transcriptional activity of the minigene reporter construct of the patient's apoc2 gene was decreased; however,no rare variant was detected in the patient's apoc2 gene. fifty single nucleotide variants were detected in the patient's apoc2,but all were common variants (allele frequencies ≥35%) that are supposedly not causative. conclusions: a case of apoc-ii deficiency was found that is phenotypically identical to hypoapoc-ii but with no causative mutations in apoc2,implying that other genes regulate apoc-ii levels. the clinical entity of hypoapoc-ii is discussed.