Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Apolipoprotein C2

Genetic mutations causing apoliproproein C2 deficiency, which is a necessary cofactor of lipoproteinlipase, result in familial chylomicronaemia.

Epidemiology

We don't know very much about the frequency of these mutations.

Gene Structure

4 apolipoproteins APOE, APOC1, APOC4, and APOC2 are located in tandem in the same direction on chromosome 19 (19q13.2). APOC4 and APOC2 can produce a conjoint gene (APOC4-APOC2). The APOC2 gene has a size of about 4kb. It consists of 4 exons. Only exons 2-4 are translated.

Phenotype

The clinical signs of lipoprotein lipase deficiency and apolipoprotein C2 defects are identical. Biochemically a hyperlipoproteinemia type I can be considered in homozygous state. In heterozygous state there is rather a mixed hyperlipimia evident. That can be type V according to classification of Fredrickson. There are often recurrent pancreatitises seen in these patients. The skin may show xanthomas.

Pathology

This apolipoprotein is a constituent of lipoproteins rich in triglyceride. This protein is an essential component for lipoproteinlipase action on triglycerides. A defect in protein has the same physiological consequences as a defect in lipoproteinlipase: the postprandial chylomikronemia is extremely prolonged.

Interpretation

This is much more easily to perform than direct mesurement in plasma. In combination with lipoprotein lipase testing it is even a much more reliable test for insufficient lipoprotein degradation. The patients have to be treated with a strong regiment of fett free diet.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Chylomicronemia
APOA5
APOC2
APOE
GPIHBP1
LPL

References:

1.

Talmud PJ et al. (2001) Genetic determinants of plasma triglycerides: impact of rare and common mutations.

[^]
2.

Fojo SS et al. (1989) A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.

[^]
3.

Tuzgöl S et al. (1994) Apolipoprotein CII-Padova (Tyr37-->stop) as a cause of chylomicronaemia in an Italian kindred from Siculiana.

[^]
Update: Sept. 26, 2018