A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in glomeruli, and an increased concentration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this disease. METHODS: An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were analyzed by isoelectric focusing and immunoblotting. Apo E genotypes were determined by restriction fragment isotyping with HhaI. Polymerase chain reaction (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7Blue-T-vector and were sequenced. RESULTS: A novel apo E mutation was identified in this patient and his family. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E gene, causing the 18-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR-amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo E1, and this mutation was determined to be the structural basis for the apo E1 phenotype. One of two daughters was a heterozygous carrier of apo E1, although she did not have proteinuria or atherosclerotic diseases. CONCLUSIONS: Apo E1 (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclerosis. The result of this family study suggests that the occurrence of LPG may involve other genetic or environmental factors.

[Surgical treatment of coarctation of the aorta and interrupted aortic arch].

From December, 1984, through April, 1987, ten infants with coarctation of the aorta and six with interrupted aortic arch underwent staged repair of aorta and other cardiac lesions. Simultaneous pulmonary artery banding was performed in six of 8 patients with ventricular septal defect (VSD) and in all of seven patients with complex cardiac lesions. With first operation, there were no operative deaths and two late deaths. Eight of 14 survivors underwent total correction of associated lesions at three to 17 months after initial operation. VSD was closed in five patients with one operative death. One patient required pulmonary artery debanding alone because of decrease of VSD size. The Damus-Kaye-Stansel operation was performed successfully in one patient with Taussig-Bing anomaly and the Jatene operation was done in one with transposition of the great arteries. Based on these results, we prefer staged repair with pulmonary artery banding for coarctation or interruption of the aorta associated with complex cardiac lesions.