ClinVar

Lohse et al. (1992) studied a kindred with apolipoprotein E deficiency and a truncated low molecular weight apoE mutant, designated apoE-3(Washington). Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Plasma apoE levels in the proband were approximately 4% of normal. This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia. Sequence analysis demonstrated a G-to-A transition which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with a molecular mass of 23.88 kD. The nucleotide substitution also resulted in the formation of a new restriction site for MaeI. Using this enzyme, they were able to establish that the proband was a homozygote and that her 2 offspring were heterozygotes. They stated that only a single kindred with apoE deficiency had been reported previously. This was the kindred reported by Ghiselli et al. (1981) and elucidated at the molecular level by Cladaras et al. (1987); see 107741.0005.