The Molecular Basis for Hereditary Porcine Membranoproliferative Glomerulonephritis Type II

Membranoproliferative glomerulonephritis (MPGN) encompasses 7 to 10% of all biopsied glomerulonephritis. They are divided in: MPGN type I; MPGN type II and MPGN type III, being primary or secondary. MPGN type I are the most frequent, MPGN types II and III are very rare and difficult to diagnose without clinical and morphologic findings integration. MPGN type II or Dense Deposit Disease has a varied morphologic appearance with a few numbers of cases showing a membranoproliferative pattern by Light microscopy (LM). Electron microscopy (EM) is pivotal to confirm the diagnosis.We present a case of 35 years old man, with nephrotic proteinuria and mild renal insufficiency since 2 years. The only relevant clinical data is facial lipodystrophy. Complement 3 (C3) was low and C3 nephritic factor negative. There were not other relevant abnormalities. Renal biopsy was fixed in buffered formaldehyde 10% and performed for LM. The frozen fragment, prepared for observation by fluorescence microscopy - immunofluorescence (IMF) -, was prepared to be stained with florescent anti-serums, against immunoglobulines (IgG, IgA and IgM) and complement factors (C3, C4, and C1q). EM was later done on tissue formaldehyde fixed reprocessed from paraffin-embebbed for LM, because there was no tissue fragment fixed in glutaraldehyde.LM showed variable endocapillary hypercelullarity, with neutrophils infiltration. Capillary walls were thickened due to the deposition of elongate and ribbon-like deposits. Few double contours were visible (Figure 1a). IMF demonstrated the presence of C3 deposits in the capillary walls and mesangium (Figure 1b). EM confirmed the presence of an intramembranous dense deposit along basement membrane which was thickened (Figure 1c). LM and IMF findings favored the diagnosis of MPGN type II with C3 deposits and thickening of basement membrane. Nevertheless EM was essential to confirm intramembranous unequivocally dense deposits.MPGN type II is a rare glomerulonephritis mediated by complement deregulation. The integration of clinical and morphologic findings is essential to get a correct diagnosis. In this setting EM is highly distinctive and required for a definitive diagnosis.

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The Molecular Basis of Antithrombin Deficiency in Belgian and Dutch Families

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615215 ◽

1998 ◽

Vol 80 (09) ◽

pp. 376-381 ◽

Cited By ~ 6

Author(s):

W. Lissens ◽

S. Seneca ◽

P. Capel ◽

B. Chatelain ◽

P. Meeus ◽

...

Keyword(s):

Molecular Basis ◽

Gene Deletion ◽

Direct Sequencing ◽

Genetic Defect ◽

Polymorphism Analysis ◽

Type I ◽

Type Ii ◽

Antithrombin Deficiency ◽

Venous Thromboembolic Events ◽

At Deficiency

SummaryThe molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed.DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intronexon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.

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