Abstract
Congenital nephrotic syndrome of the Finnish type (CNF) is inherited as an autosomal recessive trait. The biochemical basis of the disease is unknown, although a lesion in the glomerular basement membrane is strongly suggested. Recently, the CNF locus was assigned to chromosome 19q12–q13.1 on the basis of linkage analysis in Finnish families. The high incidence of the disease in Finland, as well as the demonstration of linkage disequilibrium in the Finnish study, strongly suggests a founder effect based on a common ancient mutation in this population. We confirm linkage of the CNF locus to the same chromosomal region in seven non-Finnish CNF families without evidence of linkage disequilibrium. Our results show that the same gene seems to be affected in both Finnish and non-Finnish CNF populations. However, in the latter the mutation-carrying chromosomes descend from different ancestors without evidence of a founder effect.
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References
Huttunen N-P (1976) Congenital nephrotic syndrome of Finnish type: study of 75 patients. Arch Dis Child 51:344–348
Hallman N, Norio R, Kouvalainen K (1967) Main features in the congenital nephrotic syndrome. Acta Paediatr Scand [Suppl] 172:75–77
Seppalä M, Rapola J, Huttunen N-P, Aula P, Karjalainen O, Ruoslahti E (1976) Congenital nephrotic syndrome: prenatal diagnosis and genetic counselling by estimation of amnioticfluid and maternal serum alpha-fetoprotein. Lancet II:123–125
Thom H, Johstone FD, Gibson JI, Scott GB, Noble DW (1977) Fetal proteinuria in diagnosis of congenital nephrosis detected by raised alpha-fetoprotein in maternal serum. BMJ 1:16–18
Kestilä M, Männikkö M, Holmberg C, Korpela K, Savolainen E-R, Peltonen L, Tryggvason K (1994) Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. Kidney Int 45:986–990
Kestilä M, Männikkö M, Holmberg C, Tryggvason K, Peltonen L (1994) Congenital nephrotic syndrome of the Finnish type is not associated with the Pax-2 gene despite the promising transgenic animal model. Genomics 19:570–572
Dressler GR, Douglas EC (1992) Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. Proc Natl Acad Sci USA 89:1179–1183
Kestilä M, Männikkö M, Holmberg C, Gyapay G, Weissenbach J, Savolainen E-R, Peltonen L, Tryggvason K (1994) Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19. Am J Hum Genet 54:757–764
Reed PW, Davies JL, Copeman JB, Bennet ST, Palmer SM, Pritchard LE, Gough SCL, Kawaguchi Y, Cordell HJ, Balfour KM, Jenkins SC, Powell EE, Vignal A, Todd JA (1994) Chromosome-specific microsatellite sets for fluorescence-based, semiautomated genome mapping. Nature Genet 7:390–395
Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millassean P, Marc S, Bernardi G, Lathrop M, Weissenbach J (1994) The 1993–1994 Généthon human genetic linkage map. Nature Genet 7:246–249
Lathrop GM, Lalouel JM, Julier C, Ott J (1985) Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet 37:482–498
Cottingham RW Jr, Idury RM, Schaffer AA (1993) Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263
Kruglyak L, Daly MJ, Lander ES (1995) Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet 56:519–527
Hildebrandt F, Pohlmann A, Omran H (1993) Lodview: a computer program for the graphical evaluation of lod score results in exclusion mapping of human disease genes. Comp Biomed Res 26:592–599
Nevanlinna HR (1972) The Finnish population structure — a genetic and genealogical study. Hereditas 71:195–236
Chapelle A de la (1993) Disease gene mapping in isolated human populations: the example of Finland. J Med Genet 30:857–865
Sirugo G, Keats B, Fujita R, Duclos F, Purohit K, Koenig M, Mandel JL (1992) Friedreich ataxia in Louisiana Acadians: demonstration of a founder effect by analysis of microsatellitegenerated extended haplotypes. Am J Hum Genet 50:559–566
Harley HG, Brook JD, Floyd J, Rundle SA, Crow S, Walsh KV, Thibault M-C, Harper PS, Shaw DJ (1991) Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker. Am J Hum Genet 49:68–75
Lander ES, Botstein D (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236:1567–1570
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Fuchshuber, A., Niaudef, P., Gribouval, O. et al. Congenital nephrotic syndrome of the Finnish type: linkage to the locus in a non-Finnish population. Pediatr Nephrol 10, 135–138 (1996). https://doi.org/10.1007/BF00862052
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DOI: https://doi.org/10.1007/BF00862052