Rare apolipoprotein E variant cosegregating with a unique APOE-C1-C2 haplotype in a normolipidemic family

The genes coding for the apolipoproteins E, C1 and C2 are clustered on the long arm of chromosome 19 in a region of approximately 45 kilobases (kb). In a normolipidemic individual, we detected a new apoE variant with an isoelectric point between that of E3 and E4. As this variant lacks cysteine residues and has probably arisen from an E*4 allele, it is designated E4*. To gain further insight into the origin of the mutation, the haplotypes of the propositus were extended by restriction fragment length polymorphism (RFLP) analysis of the family. The apoE variant cosegregates with the H2 allele of the HpaI polymorphism visualized with an APOE probe and with a new rare 4.5-kb fragment (T3) of the TaqI RFLP detectable with an APOC2 probe. As the propositus and the first-degree relatives with this unique haplotype are normolipidemic, this apoE variant does not seem to be associated with disturbances in the lipoprotein metabolism.