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. 1995 Jun;32(6):442–445. doi: 10.1136/jmg.32.6.442

DNA microsatellite analysis of families with autosomal dominant polycystic kidney disease types 1 and 2: evaluation of clinical heterogeneity between both forms of the disease.

E Coto 1, S Sanz de Castro 1, S Aguado 1, J Alvarez 1, M Arias 1, M J Menéndez 1, C López-Larrea 1
PMCID: PMC1050483  PMID: 7666395

Abstract

We studied 17 large families affected by adult dominant polycystic kidney disease (ADPKD). Ultrasonographic analysis was performed on all the family members. DNA microsatellite markers closely linked to PKD1 on 16p13.3 were analysed, and linkage of the disease to this locus was determined. Families showing a negative linkage value were evaluated for linkage to the PKD2 locus on 4q. Five of the 17 families showed negative linkage for the 16p13.3 markers. In these families significant linkage to 4q was obtained. Renal cysts developed at an earlier age in PKD1 mutation carriers, and end stage renal failure occurred at an older age in people affected with PKD2. Analysis of large families with ADPKD in a Spanish population indicates that this is a genetically heterogeneous disorder, but mutations at only two loci are responsible for the development of the disease in most if not all the families. Clinicopathological differences between both forms of the disease occur, with subjects with ADPKD2 having a better prognosis than those with mutations at PKD1.

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Selected References

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  1. Bear J. C., McManamon P., Morgan J., Payne R. H., Lewis H., Gault M. H., Churchill D. N. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am J Med Genet. 1984 May;18(1):45–53. doi: 10.1002/ajmg.1320180108. [DOI] [PubMed] [Google Scholar]
  2. Bear J. C., Parfrey P. S., Morgan J. M., Martin C. J., Cramer B. C. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet. 1992 Jun 1;43(3):548–553. doi: 10.1002/ajmg.1320430309. [DOI] [PubMed] [Google Scholar]
  3. Breuning M. H., Reeders S. T., Brunner H., Ijdo J. W., Saris J. J., Verwest A., van Ommen G. J., Pearson P. L. Improved early diagnosis of adult polycystic kidney disease with flanking DNA markers. Lancet. 1987 Dec 12;2(8572):1359–1361. doi: 10.1016/s0140-6736(87)91256-6. [DOI] [PubMed] [Google Scholar]
  4. Breuning M. H., Snijdewint F. G., Brunner H., Verwest A., Ijdo J. W., Saris J. J., Dauwerse J. G., Blonden L., Keith T., Callen D. F. Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1). J Med Genet. 1990 Oct;27(10):603–613. doi: 10.1136/jmg.27.10.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fenton I., Sandkuijl L. A. MEGABASE/PKD: a genetic database for polycystic kidney disease. Contrib Nephrol. 1992;97:118–127. doi: 10.1159/000421650. [DOI] [PubMed] [Google Scholar]
  6. Harris P. C., Thomas S., Ratcliffe P. J., Breuning M. H., Coto E., Lopez-Larrea C. Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker. Lancet. 1991 Dec 14;338(8781):1484–1487. doi: 10.1016/0140-6736(91)92300-q. [DOI] [PubMed] [Google Scholar]
  7. Kimberling W. J., Fain P. R., Kenyon J. B., Goldgar D., Sujansky E., Gabow P. A. Linkage heterogeneity of autosomal dominant polycystic kidney disease. N Engl J Med. 1988 Oct 6;319(14):913–918. doi: 10.1056/NEJM198810063191405. [DOI] [PubMed] [Google Scholar]
  8. Kimberling W. J., Kumar S., Gabow P. A., Kenyon J. B., Connolly C. J., Somlo S. Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics. 1993 Dec;18(3):467–472. doi: 10.1016/s0888-7543(11)80001-7. [DOI] [PubMed] [Google Scholar]
  9. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  10. Parfrey P. S., Bear J. C., Morgan J., Cramer B. C., McManamon P. J., Gault M. H., Churchill D. N., Singh M., Hewitt R., Somlo S. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med. 1990 Oct 18;323(16):1085–1090. doi: 10.1056/NEJM199010183231601. [DOI] [PubMed] [Google Scholar]
  11. Peral B., Ward C. J., San Millán J. L., Thomas S., Stallings R. L., Moreno F., Harris P. C. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease I population. Am J Hum Genet. 1994 May;54(5):899–908. [PMC free article] [PubMed] [Google Scholar]
  12. Peters D. J., Spruit L., Saris J. J., Ravine D., Sandkuijl L. A., Fossdal R., Boersma J., van Eijk R., Nørby S., Constantinou-Deltas C. D. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet. 1993 Dec;5(4):359–362. doi: 10.1038/ng1293-359. [DOI] [PubMed] [Google Scholar]
  13. Ravine D., Gibson R. N., Walker R. G., Sheffield L. J., Kincaid-Smith P., Danks D. M. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994 Apr 2;343(8901):824–827. doi: 10.1016/s0140-6736(94)92026-5. [DOI] [PubMed] [Google Scholar]
  14. Reeders S. T., Breuning M. H., Corney G., Jeremiah S. J., Meera Khan P., Davies K. E., Hopkinson D. A., Pearson P. L., Weatherall D. J. Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16. Br Med J (Clin Res Ed) 1986 Mar 29;292(6524):851–853. doi: 10.1136/bmj.292.6524.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reeders S. T., Breuning M. H., Davies K. E., Nicholls R. D., Jarman A. P., Higgs D. R., Pearson P. L., Weatherall D. J. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. doi: 10.1038/317542a0. [DOI] [PubMed] [Google Scholar]
  16. Romeo G., Devoto M., Costa G., Roncuzzi L., Catizone L., Zucchelli P., Germino G. G., Keith T., Weatherall D. J., Reeders S. T. A second genetic locus for autosomal dominant polycystic kidney disease. Lancet. 1988 Jul 2;2(8601):8–11. doi: 10.1016/s0140-6736(88)92943-1. [DOI] [PubMed] [Google Scholar]
  17. Somlo S., Wirth B., Germino G. G., Weinstat-Saslow D., Gillespie G. A., Himmelbauer H., Steevens L., Coucke P., Willems P., Bachner L. Fine genetic localization of the gene for autosomal dominant polycystic kidney disease (PKD1) with respect to physically mapped markers. Genomics. 1992 May;13(1):152–158. doi: 10.1016/0888-7543(92)90215-e. [DOI] [PubMed] [Google Scholar]
  18. Thompson A. D., Shen Y., Holman K., Sutherland G. R., Callen D. F., Richards R. I. Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16. Genomics. 1992 Jun;13(2):402–408. doi: 10.1016/0888-7543(92)90260-y. [DOI] [PubMed] [Google Scholar]
  19. Wright G. D., Hughes A. E., Larkin K. A., Doherty C. C., Nevin N. C. Genetic linkage analysis, clinical features and prognosis of autosomal dominant polycystic kidney disease in Northern Ireland. Q J Med. 1993 Jul;86(7):459–463. [PubMed] [Google Scholar]

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