Molecular cloning of the critical region for glomerulopathy with fibronectin deposits (GFND) and evaluation of candidate genes.

Abstract:

:Glomerulopathy with fibronectin deposits (GFND, MIM 601894) is an autosomal dominant kidney disease that leads to terminal renal failure at a median age of 47 years. It represents a distinct entity of membranoproliferative glomerulonephritis (MPGN) type III and is characterized by the unique feature of massive glomerular deposits of fibronectin. We have recently localized a gene locus for GFND to human chromosome 1q32 by total genome linkage analysis in a large kindred, within a 4.1-cM critical interval between markers D1S2872 and D1S2891. This interval contains a cluster of genes for "regulators of complement activation" (RCA), which represent strong candidates for GFND. To identify positional candidate genes for GFND within the critical genetic interval, we here report the cloning of the entire critical GFND region in a complete YAC and partial PAC contig. We constructed a high-resolution transcriptional map, thereby defining positional and functional candidate genes for the disease. To evaluate their role in GFND, we performed functional studies on RCA proteins in GFND patients from the large kindred, as well as mutational analysis of the genes for complement receptor-2 (CR2), membrane cofactor protein (MCP), and decay accelerating factor (DAF). Although no loss-of-function mutation has been identified as yet, these data provide a basis for the examination of candidate genes for GFND and other genes for MPGN, which localize to the vicinity of the GFND region.

journal_name

Genomics

journal_title

Genomics

authors

Vollmer M,Kremer M,Ruf R,Miot S,Nothwang HG,Wirth J,Otto E,Krapf R,Hildebrandt F

doi

10.1006/geno.2000.6292

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

127-35

issue

2

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(00)96292-X

journal_volume

68

pub_type

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