K. Konishi et al., Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy, NEPHRON, 83(3), 1999, pp. 214-218
Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease charac
terized by abnormal lipoprotein deposition in the glomeruli, dysbetalipopro
teinemia, and a high level of plasma apolipoprotein (apo) E. We identified
a novel apo E mutation in a 56-year-old Japanese male with LPG. Although th
e plasma cholesterol and triglyceride levels were normal, the levels of int
ermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/
dl (0.336 mmol/l; 4.2+/-2.9 mg/dl, mean +/- SD, in 12 normolipidemic contro
ls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual a
po E phenotype (E1/3), Apo E genotyping using DNA digested by a restriction
enzyme (Hhal) identified a 66-bp fragment which was not seen with any of t
he common alleles. Sequence analysis of the amplified genomic DNA fragments
showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino
acid deletion (residues 141-143). This novel mutation involves the region o
f the apo E molecule known to be critically involved in binding to its rece
ptor, and this may well transform the apo E molecule, an inefficient ligand
, to its receptor(s). How this mutations causes glomerular damage remains t
o be determined.