Scientific background:

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

Gene: The gene APOC2 has a size of about 4kb and is located on chromosom 19 (19q13.2). It consists of 4 exons. Only 3 of them will be translated.

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.

Clinical signs: 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.

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

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.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Fojo SS et al. (1989) A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.
Tuzgöl S et al. (1994) Apolipoprotein CII-Padova (Tyr37-->stop) as a cause of chylomicronaemia in an Italian kindred from Siculiana.
Talmud PJ et al. (2001) Genetic determinants of plasma triglycerides: impact of rare and common mutations.