{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:02:37Z","timestamp":1771002157450,"version":"3.50.1"},"reference-count":22,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/jmg.32.6.442","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"442-445","source":"Crossref","is-referenced-by-count":10,"title":["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."],"prefix":"10.1136","volume":"32","author":[{"given":"E","family":"Coto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Sanz de Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Aguado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Arias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M J","family":"Men\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"L\u00f3pez-Larrea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1995,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/ajmg.1320180108","article-title":"Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling","volume":"18","author":"Bear, J.C.; McManamon, P.; Morgan, J.","year":"1984","unstructured":"Bear JC, McManamon P, Morgan J, et al. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am _7 Med Genet 1984;18:45-53.","journal-title":"Am _7 Med Genet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajmg.1320430309","article-title":"Autosomal dominant polycystic kidney disease: new information for genetic counselling","volume":"43","author":"Bear, J.C.; Parfrey, P.S.; Morgan, J.M.; Martin, C.J.; Cramer, B.C.","year":"1992","unstructured":"Bear JC, Parfrey PS, Morgan JM, Martin CJ, Cramer BC. Autosomal dominant polycystic kidney disease: new information for genetic counselling. 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Fine genetic localization of the gene for autosomal dominant polycystic kidney disease (PKD1) with respect to physically mapped markers. Genomics 1992;13:152-8.","journal-title":"Genomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/0092-8674(94)90137-6","article-title":"The European Polycystic Kidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16","volume":"77","year":"1994","unstructured":"The European Polycystic Kidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. 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J Med Genet 1990;27:603-13.","journal-title":"J Med Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/0140-6736(91)92300-Q","article-title":"Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker","volume":"338","author":"Harris, P.C.; Thomas, S.; Ratcliffe, P.J.; Breuning, M.H.; Coto, E.; L6pez-Larrea, C.","year":"1991","unstructured":"Harris PC, Thomas S, Ratcliffe PJ, Breuning MH, Coto E, L6pez-Larrea C. Rapid genetic analysis of families with polycystic kidney disease 1 by means of a microsatellite marker. Lancet 1991;338:1484-7.","journal-title":"Lancet"},{"key":"ref_10","first-page":"899","article-title":"Evidence of linkage disequilibrium in the Spanish polycystic kidney disease I population","volume":"54","author":"Peral, B.; Ward, C.J.; San Millan, J.L.","year":"1994","unstructured":"Peral B, Ward CJ, San Millan JL, et al. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease I population. Ami _7 Hum Genet 1994;54:899-908.","journal-title":"Ami _7 Hum Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/ng1293-359","article-title":"Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease","volume":"5","author":"Peters, D.J.M.; Spruit, L.; Saris, J.J.","year":"1993","unstructured":"Peters DJM, Spruit L, Saris JJ, et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. 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N Engl _r Med 1990;323:1085-90.","journal-title":"N Engl _r Med"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/0888-7543(92)90260-Y","article-title":"Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16","volume":"13","author":"Thompson, A.D.; Shen, Y.; Holman, K.; Sutherland, G.R.; Callen, D.F.; Richards, R.I.","year":"1992","unstructured":"Thompson AD, Shen Y, Holman K, Sutherland GR, Callen DF, Richards RI. Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16. Genomics 1992;13:402-8.","journal-title":"Genomics"},{"key":"ref_18","first-page":"460","article-title":"Easy calculations of lod scores and genetic risks on small computers","volume":"36","author":"Lathrop, G.M.; Lalouel, J.M.","year":"1984","unstructured":"Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers. Am _7 Hum Genet 1984;36:460-5.","journal-title":"Am _7 Hum Genet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1159\/000421650","article-title":"Megabase\/PKD: a genetic database for polycystic kidney disease","volume-title":"to nephrology 97. Polycystic kidney disease","author":"Fenton, I.; Sandkuijl, L.A.","year":"1992","unstructured":"Fenton I, Sandkuijl LA. Megabase\/PKD: a genetic database for polycystic kidney disease. In: Breuning MH, Devoto M, Romeo G, eds. Contributions to nephrology 97. Polycystic kidney disease. Basel: Karger, 1992:118-27."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/S0140-6736(94)92026-5","article-title":"Evaluation of ultrasonographic diagnosis criteria for autosomal dominant polycystic kidney disease 1","volume":"343","author":"Ravine, D.; Gibson, R.N.; Walker, R.G.; Sheffield, L.J.; KincaidSmith, P.; Danks, D.M.","year":"1994","unstructured":"Ravine D, Gibson RN, Walker RG, Sheffield LJ, KincaidSmith P, Danks DM. Evaluation of ultrasonographic diagnosis criteria for autosomal dominant polycystic kidney disease 1. Lancet 1994;343:824-7.","journal-title":"Lancet"},{"key":"ref_21","first-page":"243","article-title":"Genetic and clinical studies in autosomal dominant polycystic kidney disease type I","volume":"29","author":"Coto, E.; Aguado, S.; Alvarez, J.; Menendez, M.J.; Lopez-Larrea, C.","year":"1992","unstructured":"Coto E, Aguado S, Alvarez J, Menendez MJ, Lopez-Larrea C. Genetic and clinical studies in autosomal dominant polycystic kidney disease type I (ADPKD 1)..7 Med Genet 1992;29:243-6."},{"key":"ref_22","first-page":"459","article-title":"Genetic linkage analysis, clinical features and prognosis of autosomal dominant polycystic kidney disease in Northern Ireland","volume":"86","author":"Wright, G.D.; Hughes, A.E.; Larkin, K.A.; Doherty, C.C.; Nevin, N.C.","year":"1993","unstructured":"Wright GD, Hughes AE, Larkin KA, Doherty CC, Nevin NC. Genetic linkage analysis, clinical features and prognosis of autosomal dominant polycystic kidney disease in Northern Ireland. 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