Heterozygous apolipoprotein C-II deficiency: lipoprotein and apoprotein phenotype and RsaI restriction enzyme polymorphism in the Apo C-IIPadova kindred.
Deficiency of apolipoprotein C-II (apo C-II), the cofactor for lipoprotein lipase, results in the familial chylomicronaemia syndrome characterized by severe hypertriglyceridaemia and fasting chylomicronaemia. To investigate the biochemical features of the heterozygous state for apo C-II deficiency, we characterized the lipid, lipoprotein and apolipoprotein profiles in 18 relatives of two affected individuals (brother and sister) homozygous for the apo C-IIPadova gene defect which results in the synthesis of a truncated 36 amino acid apolipoprotein. Carrier status was established in first degree relatives as well as in seven non-obligate heterozygotes by restriction enzyme analysis of amplified apo C-II genomic DNA using RsaI. No significant differences in lipid, lipoprotein and apo C-II levels were observed in heterozygotes when compared to unaffected family members. Thus, in this study, the carrier state was not associated with hypertriglyceridaemia or reduced plasma levels of apo C-II. However, analysis of amplified DNA from members of the apo C-IIPadova kindred by digestion with the enzyme RsaI, which identifies the mutant apo C-II, permitted the identification of heterozygous family members which could not be recognized by measuring either fasting triglycerides or plasma apo C-II levels. This study provides further evidence that apo C-II deficiency syndrome is a heterogeneous disease not only at the molecular level but also on the clinical ground with variable phenotypic expression in heterozygous individuals from different kindreds.
Gabelli
C
C
Department of Internal Medicine, University of Padova, Italy.
Bilato
C
C
Santamarina-Fojo
S
S
Martini
S
S
Brewer
H B
HB
Crepaldi
G
G
Baggio
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D005190:Family; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D008055:Lipids; D008074:Lipoproteins