Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is one of the major hereditary nephropathies in children predominantly presenting in early childhood. The clinical picture is variable but there is a fatal outcome in many cases. We have performed linkage analysis in 16 ARPKD families and localized the ARPKD gene to chromosomal region 6p21–cen with no evidence for genetic heterogeneity among different clinical phenotypes. Linkage was confirmed using six adjacent microsatellite markers and the highest lod score of 7.42 was obtained with D6S272 at θ=0.00. Our findings should lead to more accurate forms of prenatal diagnosis than those currently available using ultrasound.
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References
Zerres, K., Rudnik-Schönebom, S. & Deget, F. Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. J. med. Genet. 30, 583–588 (1993).
Cole, B.R. Autosomal recessive polycystic kidney disease. In The cystic kidney (eds K.D. Gardner & J. Bernstein) 326–350 (Kluwer Academic Publishers, Dordrecht, London, Boston, 1990).
Reeders, S.T. et al. A higly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature 317, 543–544 (1985).
Romeo, G. et al. A second genetic locus for autosomal dominant polycystic kidney disease. Lancet 2, 8–10 (1988).
Kimberling, W.J. et al. Linkage heterogeneity of autosomal domlnant polycystlc kidney disease. New Engl. J. Med. 319, 913–917 (1988).
Pafrey, P.S. et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. New Engl. J. Med. 323, 1085–1090 (1990).
Kimberling, W.J. et al. Autosomal dominant polycystic kidney disease: localization of the second gene to chromoosme 4q13–q23. Genomics 18, 467–472 (1993).
Peters, D.J.M. et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nature Genet. 5, 359–362 (1993).
Zerres, K., Hansmann, M., Mallmann, R., Gembruch, U. Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis. Prenat. Diag. 8, 215–229 (1988).
Neumann, H.P.M. et al. Late manifestation of autosomal-recessive polycystic kidney disease in two sisters. Am. J. Nephrol. 8, 194–197 (1988).
Blyth, H. & Ockenden, B.G. Polycystic disease of kidneys and liver presenting in childhood. J. med. Genet. 8, 257–284 (1971).
Zerres, K. Autosomal recessive polycystic kidney disease. J. clin. Invest. 70, 794–801 (1992).
Kaplan, B.S., Fay, J., Shah, V., Dillon, M.J. & Barratt, T.M. Autosomal recessive polycystic kidney disease. Pediatr. Nephrol. 3, 43–49 (1989).
Zerres, K., Vöipel, M.C. & Weiß, H. Cystic kidneys. Genetics, pathologic anatomy, clinical picture and prenatal diagnosis. Hum. Genet. 68, 104–135 (1984).
Hildebrandt, F., Pohlmann, A. & Omran, H. 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 (1993).
Matise, T.C., Perlin, M. & Chakravarti, A. Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genet. 6, 384–390 (1994).
Wirth, B. et al. Autosomal recessive and dominant forms of polycystic kidney disease are not allelic. Hum. Genet. 77, 221–222 (1987).
Zerres, K., Mücher, G. & Rudnik-Schöneborn, S. Autosomal recessive polycystic kidney disease does not map to the second gene locus for autosomal dominant polycystic kidney disease on chromosome 4. Hum. Genet. (in the press).
Guay-Woodford, L.M., D'Eustachio, P., Mücher, G., Uhlhaas, S. & Zerres, K. Testing the hypothesis that murine congenital polycystic kidney disease (cpk) and human autosomal recessive polycystic kidney disease (ARPKD) affect homologous genes. J. Am. Soc. Nephrol. 1, 300A (1990).
Kwiatkowski, T.J., Beaudet, A.L., Trask, B.J. & Zoghbi, H.Y. Linkagemapping and fluorescence in situ hybridisation of TCTE1 on human chromosome 6p: Analysis of dlnucleotide polymorphisms on native gels. Genomics 10, 921–926 (1991).
Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).
Brzustowicz, L.M. et al. Genetic mapping of chronic childhood-onset spinal atrophy to chromosome 5q11.2–13.3. Nature 344, 540–541 (1990).
Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular cloning: A laboratory manual 2nd edn (Cold Spring Harbor Laboratory, New York 1989).
Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: Detection of linkage and estimation in humans: Detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).
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Zerres, K., Mücher, G., Bachner, L. et al. Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21–cen. Nat Genet 7, 429–432 (1994). https://doi.org/10.1038/ng0794-429
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DOI: https://doi.org/10.1038/ng0794-429
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