Laboratory Investigation

Kidney International (1994) 45, 986–990; doi:10.1038/ki.1994.133

Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type

Marjo Kestilä, Minna Männikkö, Christer Holmberg, Kaija Korpela, Eeva-Riitta Savolainen, Leena Peltonen and Karl Tryggvason

Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu; Department of Human Molecular Genetics, National Public Health Institute, and Children's Hospital, University of Helsinki, Helsinki; and Department of Clinical Chemistry, University of Oulu, Oulu, Finland

Correspondence: Karl Tryggvason MD PhD, Biocenter Oulu and Department of Biochemistry, University of Oulu, FIN-90570 Oulu, Finland.

Received 9 September 1993; Revised 12 November 1993; Accepted 18 November 1993.

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Abstract

Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. The congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria already at birth. The gene locus defective in CNF was searched for using polymorphic markers of candidate genes coding for components of the basement membrane (BM). The linkage analyses in 17 Finnish CNF families demonstrated exclusion or obligatory recombination events between the disease and eight genes coding for BM components. The genes coding for the alpha1(IV), alpha2(IV), alpha3(IV) and alpha4(IV) chain of type IV collagen, the B1e, B2e and B2t chains of laminin, as well as the BM heparan sulfate proteoglycan core protein were all excluded in this Finnish family material. Since the defect is not in any of the genes coding for major components of BM, the identification of the gene defect will most probably reveal a new gene important for the development and function of the glomerular basement membrane.

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