caa a22 4500 39757438X CHVBK 20180308164851.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/hmg/5.4.539 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.4.539 A Stable, Nonsense Mutation Associated with a Case of Infantile Onset Polycystic Kidney Disease 1 (PKD1) [Elektronische Daten] [Belén Peral, Albert C. M. Ong, José L. San Millân, Vicki Gamble, Lesley Rees, Peter C. Harris] Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novochange in the father, and of grandpaternal origin. PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycys-tic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder. © 1996 Oxford University Press Peral Belén MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Ong Albert C. M. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut San Millân José L. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Gamble Vicki MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Rees Lesley Department of Paediatric Nephrology, Royal Free Hospital, London NW3 2QG, UK aut Harris Peter C. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut Human Molecular Genetics Oxford University Press 5/4(1996-04), 539-542 0964-6906 5:4<539 1996 5 hmg https://doi.org/10.1093/hmg/5.4.539 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.4.539 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Peral Belén MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- Ong Albert C. M. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- San Millân José L. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- Gamble Vicki MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 700 1- Rees Lesley Department of Paediatric Nephrology, Royal Free Hospital, London NW3 2QG, UK aut NATIONALLICENCE 700 1- Harris Peter C. MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/4(1996-04), 539-542 0964-6906 5:4<539 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford