Apolipoprotein E*3-Leiden allele results from a partial gene duplication in exon 4.
The apolipoprotein E3-Leiden variant has been shown to be associated with familial dysbetalipoproteinemia (FD) in a dominant manner (Havekes et al., Hum Genet 1986;73:157-163). Applying the polymerase chain reaction technique, we have cloned and sequenced relevant parts of both APOE alleles of the original proband. In exon 4 of the E*3-Leiden allele a partial gene duplication encompassing 21 nucleotides was found, leading to a tandem repeat of the codons 120-126 or 121-127. Using an E3-Leiden mutation specific oligonucleotide probe, the same mutation was found in two additional independently ascertained FD patients with an E3E3 phenotype based on isoelectric focusing. The E*3-Leiden mutation will be useful in the elucidation of the etiology of dominantly inherited forms of FD.
van den Maagdenberg
A M
AM
Department of Human Genetics, State University Leiden, The Netherlands.
de Knijff
P
P
Stalenhoef
A F
AF
Gevers Leuven
J A
JA
Havekes
L M
LM
Frants
R R
RR
D000595:Amino Acid Sequence; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons; D005796:Genes; D005799:Genes, Dominant; D014644:Genetic Variation; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D015345:Oligonucleotide Probes; C052720:apolipoprotein E3 (Leidein)