Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family.
Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle.
Patel
S
S
Department of Medicine, Royal Post-graduate Medical School, London, UK.
Pessah
M
M
Beucler
I
I
Navarro
J
J
Infante
R
R
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000235:genetics*; D002914:Chylomicrons / Q000097:blood*; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics*
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D018076:DNA, Complementary; D012333:RNA, Messenger