Inheritance of a Stable Mutation in a Family with Early-Onset DiseasePerrichot R.A.a,d · Mercier B.d · de Parscau L.c · Simon P.M.b · Cledes J.a · Ferec C.d
Services de Néphrologie,aCHU Brest, bCH Saint-Brieuc, cService de Pédiatrie, CHU Brest, dLaboratoire de Génétique moléculaire, CHU Brest, France
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Autosomal/dominant polycystic kidney disease (ADPKD) exhibits a high inter- and intrafamilial heterogeneity partly explained by the involvement of at least 3 different genes in the disorder transmission. PKD1, the major locus, is located on chromosome 16p. The occurrence of very early-onset cases of ADPKD (sometimes in utero) in a few PKD1 families or the increased severity of the disease in successive generations raise the question of anticipation. This is a subject of controversial discussion. This report deals with the molecular analysis in families with very early-onset ADPKD. The finding of the same stable mutation with such different phenotypes rules out a dynamic mutation. The molecular basis of severe childhood PKD in typical ADPKD families remains unclear; it may include segregation of modifying genes or unidentified factors and the two-hit mechanism.
© 2001 S. Karger AG, Basel
Dalgaard OZ: Bilateral polycystic disease of the kidney: A follow-up of two hundred and eighty-four patients and their families. Acta Med Scand 1957;158:328–381.
Peters DJM, Sandkuijl LA: Genetic heterogeneity of polycystic kidney disease in Europe. Contrib Nephrol. Basel, Karger, 1992, vol 97, pp 128–139.
- 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. Cell 1994;77:881–894.
- Kimberling WJ, Kumar R, Gabow PA, Kenyon JB, Connoly CJ, Somlo S: Autosomal dominant polycystic kidney disease: Localisation of the second gene to chromosome 4q13–23. Genomics 1993;18:467–472.
- Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhusien B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Kimberling WJ, Breuning M, Deltas C, Peters D, Somlo S: PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 1996;272:1339–1342.
- De Almeida S, De Almeida E, Peters DJM, Pinto JR, Tavora I, Lavinha J, Breuning M, Prata M: Autosomal dominant polycystic kidney disease: Evidence for the existence of a third locus in a Portuguese family. Hum Genet 1995;96:83–88.
- Ariza M, Alvarez V, Marin R, Aguado S, Lopez-Larrea C, Alvarez J, Menendes MJ, Coto E: A family with a milder form of adult dominant polycystic kidney disease not linked to the PKD(16p) or PKD2(4q) genes. J Med Genet 1997;34:587–589.
- Ravine D, Walker RG, Gibson RN, Forrest SM, Richards RI, Friend K, Sheffield LJ, Kinkaid-Smith P, Danks DM: Phenotype and genotype heterogeneity in autosomal-dominant polycystic kidney disease. Lancet 1992;340:1330–1333.
- Zerres K, Rudnick-Schöneborn S: On genetic heterogeneity, anticipation, and imprinting in polycystic kidney disease. Nephrol Dial Transplant 1995;10:7–9.
- Fick GM, Johhson AM, Gabow PA: Is there evidence for anticipation in autosomal-dominant polycystic kidney disease? Kidney Int 1994;45:1153–1162.
- Hateboer N, Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D: Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 1999;353:103–107.
- Hateboer N, Lazarou A, Williams A, Holmans P, Ravine D: Familial phenotype differences in PKD1. Kidney Int 1999;56:34–40.
- Peral B, San Millan JL, Ong ACM, Gamble V, Ward CJ, Strong C, Harris PC: Screening the 3′ region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations. Am J Hum Genet 1996;58:86–96.
- Peral B, Gamble V, Strong C, Sloane-Stanley J, Zerres K, Winearls CG, Harris PC: Identification of mutations in the duplicated region of the polycystic kidney disease-1 (PKD1) gene by a novel approach. Am J Hum Genet 1997;60:1399–1410.
Turco A, Bresin E, Rossetti S, English S, Pignatti PF, Gammaro L, Maschio G, Bendetti M, Li Vecchi M, Ferantelli A, Cerasola G, Stiasny B, Schulze B: Molecular genetic investigations in autosomal-dominant polycystic kidney disease. Contrib Nephrol. Basel, Karger, 1997, vol 122, pp 53–57.
- Badenas C, Torra R, San Millan JL, Lucero L, Mila M, Estivill X, Darnell A: Mutational analysis within the 3′ region of the PKD1 gene. Kidney Int 1999;55:1225–1233.
Daniells C, Maheshwar MM, Lazarou L, Davies F, Coles G, Ravine D: Novel and recurrent mutations in the PKD1 (polycystic kidney disease). Gene Hum Genet 1998;102:216–220.
- Watnick T, Pontiek KB, Cordal TM, Weber H, Gandolph MA, Lens XM, Neumann HP, Germino GG: An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection. Hum Mol Genet 1997;6:1473–1481.
- Roelfsema JH, Spruit L, Saris JJ, Chang P, Pirson Y, Van Ommen GJB, Peters DJM, Breuning M: Mutation detection in the repeated part of PKD1 gene. Am J Hum Genet 1997;61:1044–1052.
- Thomas R, McConnell R, Whittacker J, Kirkpatrick P, Bradley J, Sandford R: Identification of mutations in the repeated part of the autosomal-dominant polycystic kidney disease type I gene, PKD1, by long-range PCR. Am J Hum Genet 1999;65:39–49.
- Perrichot R, Mercier B, Simon P, Whebe B, Cledes J, Férec C: DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients. Hum Genet 1999;105:231–239.
- Perrichot R, Mercier B, Quere I, Carre A, Simon P, Whebe B, Cledes J, Férec C: Novel mutations in the duplicated region of the PKD1 gene. Eur J Hum Genet 2000;8:353–359.
Gabow PA: Definition and natural history of autosomal-dominant polycystic kidney disease in polycystic kidney disease. Clin Nephrol 1996;332–355.
- Geberth S, Ritz E, Zeier M, Stier E: Anticipation of age at renal death in autosomal-dominant polycystic kidney disease? Nephrol Dial Transplant 1995;10:1603–1660.
Torra R, Badenas C, Peral B, Darnell A, Gamble V, Turco A, Harris PC, Estivill X: Recurrence of the PKD1 nonsense mutation Q4041X in Spanish , Italian and British families. Hum Mutat 1998;(suppl 1):117–120.
- Watnick T, Phakdeekitcharoen B, Johhson A, Gandolph MA, Wang M, Briefel G, Klinger KW, Kimberling W, Gabow P, Germino GG: Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very early disease. Am J Hum Genet 1999;65:1561–1571.
Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes JM, Maheshwar MM, Nellist M, Gamble V, Harris PC, Sampson J: Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease. A contiguous gene syndrome. Nature 1994;8:328–332.
Fick G, Johhson A, Strain J, Kimberling W, Kumar S, Manco-Johnson, Duley I, Gabow P: Characteristics of very early onset autosomal-dominant polycystic kidney disease. J Am Soc Nephrol 1999;12:1863–1870.
- Zerres K, Rudnick-Schöneborn S, Deget F, and Members of the German Working Group on Paediatric Nephrology: Childhood onset of autosomal polycystic kidney disease in sibs: Clinical picture and recurrence risk. J Med Genet 1993;30:583–588.
- McDermot K, Saggar-Malik AK, Economides D, Jeffery S: Prenatal diagnosis of autosomal-dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease. J Med Genet 1998;35:13–16.
- Peral B, Ong ACM, San Millan JL, Gamble V, Rees L, Harris PC: A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). Hum Mol Genet 1996;5:539–542.
- Torra R, Badenas C, Darnell A, Bru C, Escorsell A, Estivill X: Autosomal-dominant polycystic kidney disease with anticipation of Caroli’s disease associated with PKD1 mutation. Kidney Int 1997;52:33–38.
- Richards RI, Sutherland GR: Dynamic mutations: A new class of mutations causing human disease. Cell 1992;70:709–712.
- The Huntington‘s Disease Collaborative Research Group: A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington disease chromosomes. Cell 1993;72:971–983.
- Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warren ST, Schlessinger D, Sutherland GR, Richards RI: Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 1991;252:1711–1714.
- Burn TC, Connors TD, Dackowski WR, Petry LR, Van Raay TJ, Millholland JM, Venet M, Miller G, Hakim RM, Landes GM, Klinger KW, Qian F, Onuchic LF, Watnick T, Germino GG, Dogget NA: Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. Hum Mol Genet 1995;4:575–582.
- Qian F, Watnick T, Onuchic LF, Germino GG: The molecular basis of focal cyst formation in human autosomal-dominant polycystic kidney disease type 1. Cell 1996;87:979–987.
- Brasier JL, Henske EP: Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest 1997;99:194–199.
- Torra R, Badenas C, San Millan JL, Perres-Oller L, Estivill X, Darnell A: A loss-of-function model for cystogenesis in human autosomal-dominant polycystic kidney disease type 2. Am J Hum Genet 1999;65:345–352.
- Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino GG, St George-Hyslop P: Somatic PKD2 mutations in individual kidney and liver cysts support a two-hit model of cystogenesis in type 2 autosomal polycystic kidney disease. J Am Soc Nephrol 1999;10:1524–1529.
Koptides M, Hadjimichael C, Koupepidou P, Pierides A, Deltas C: Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal-dominant polycystic kidney disease. Hum Mol Genet 1999;3:509–513.
Deltas C, Mean R, Kyriakides G, Hadjigavriel M, Demetriou K, Pierides A, Koptides M: Genetic evidence for cooperative interaction of polycystins 1 and 2, which are mutated in polycystic kidney disease (ADPKD). Am J Hum Genet 1999;66(suppl):A108–A571.
- Laboukova O, Dushkin H, Beier D: Localization of a murine recessive polycystic kidney disease mutation and modifying loci that affect disease severity. Genomics 1995;26:107–114.
- Woo D, Nguyen D, Hatibin K, Olsen P: Genetic identification of two modifier loci of polycystic kidney disease progression in pcy mice. J Clin Invest 1997;100:1934–1940.
- O’Sullivan D, Torres V, Gabow P, Thibodeau S, King B, Bergstrahl E: Cystic fibrosis and the phenotypic expression of autosomal-dominant polycystic kidney dysease. Am J Kidney Dis 1998;32:976–983.
- Qian F, Germino FJ, Cai Y, Zhang X, Somlo S, Germino GG: PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet 1997;16:179–183.
- Tsiokas L, Kim E, Arnould T, Sukhame VP, Walz G: Homo- and heterodimeric interactions between the genes product of PKD1 and PKD2. Proc Natl Acad Sci USA 1997;94:6965–6970.
- Zerres K, Mucher G, Bachner L, Deschennes G, Eggermann T, Kaarianen H, Knapp M, Lennert T, Misselwitz J, von Mühlendahl K, Neumann Y, Pirson Y, Rudnick-Schöneborn S, Steinbicker V, Wirth B, Schärer K: Mapping of the gene for autosomal-recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen. Nat Genet 1994;7:429–432.
- Yoder B, Wilkinson J, Avner E, Woychickr RP: The Tg737 protein interacts with polycystine and proteins controlling epithelial polarity, EGFR stability and cellular differentiation. J Am Soc Nephrol 1997;8:386A.
Verlingue C, David A, Audrézet MP, Le Roux MG, Mercier B, Moisan JP, Férec C: Asymptomatic carrier of two CFTR mutations: Consequences for prenatal diagnosis? Prenatl Diagn 1993;13:1143–1148.
- Savov A, Angelicheva D, Balassopoulou A, Jordanova N, Noussia-Arvanitakis S, Kalaydjieva L: Double mutants alleles: Are they rare? Hum Mol Genet 1995;4:1169–1171.
Levy M, Duyme M, Serbelloni P, Conte F, Sessa A, Grunfeld JP: Is progression of renal involvement similar in twins with ADPKD? A multicentric European Study. Contrib Nephrol. Basel, Karger, 1995, vol 115, pp 65–71.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.