CHYLOMICRON RETENTION DISEASE - EXCLUSION OF APOLIPOPROTEIN-B GENE DEFECTS AND DETECTION OF MESSENGER-RNA EDITING IN AN AFFECTED FAMILY

Chylomicron retention disease (CRD) is a rare autosomal recessive diso rder characterized by the absence of postprandial chylomicrons and apo lipoprotein (ape) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in ser a. A crucial difference between the synthesis and secretion of apo B-c ontaining 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 rep resent an absence of editing of apo B mRNA in the gut was investigated . Two affected sisters were identified as having low cholesterol level s and an absence of post-prandial chylomicronemia. Segregation analysi s in the family showed that the apo B locus is not the site of the def ect. Using reverse transcription-polymerase chain reaction (RT-PCR), d uodenal biopsy-mRNA from the affected sisters was isolated and analyze d. 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 provid es strong confirmation that the primary defect in CRD is not in the sy nthesis, or editing of ape B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secreti on of the chylomicron particle.