APOLIPOPROTEIN B (APO B) GENE IN CONGENITAL DISORDERS OF FAT ABSORPTION

Abstract

The aim of the present study was to elucidate whether the great heterogeneity of biochemical lesions responsible for abetalipoproteinemia (ablp) and Anderson's disease (Ad) resulted from different types of genetic alterations. 4 patients with Ad (SZ, YZ, KZ and MK) and 2 with ablp (MP and SL) were studied. Earlier studies had shown that the enterocytes from the 4 Ad cases and from SL, but not from MP, contained (abnormal ?) apo B 48. DNA from these patients and from 3 normal subjects was prepared from their leucocytes. The following cDNA probes, covering the whole apo B gene, were used; A6c, ABF, AB1, RP2 and SB9, of 3,5, 6,5, 5,1, 0,3, and 6 kb respectively. DNA was treated with the following restriction enzymes : XbaI, PvuII, MspI, EcoRI, HINDIII, HinfI and TaqI and subsequently analysed on Southern blots. Restriction fragment patterns differed greatly among the patients. SL and MP were heterozygotes for an EcoRI polymorphism at residue 4154 of mature apo B. SL, SZ, YZ, KZ were homozygotes for the 8,6 kb allele produced by XbaI while MP was heterozygote for the same allele and MK was homozygote for the 5,5 kb allele produced by the same enzyme. No major deletion or rearrangement of apo B gene could be found in any of the 6 patients. In conclusion : 1) ablp and Ad seem not to be associated with a particular apoB allele, and 2) only a closer study of apo B gene will show the different mutations responsible for the diseases.