Genetic Heterogeneity in Wilson Disease: Lessons from Rare Alleles
Authors: Reed Edwin Pyeritz
Journal: Annals of Internal Medicine (1997)

Editorials1 July 1997Genetic Heterogeneity in Wilson Disease: Lessons from Rare AllelesReed Edwin Pyeritz, MD, PhDReed Edwin Pyeritz, MD, PhDMCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Pittsburgh, PA 15212.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-1-199707010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In 1912, S.A. Kinnier Wilson (1877-1937) described the condition that now bears his name [1, 2]. As a neurologist, he was interested in the progressive deterioration of the nervous system seen with this condition, but the involvement of the liver and the familial clustering of cases also intrigued him. In the previous decade, Mendel's laws had been rediscovered and Garrod had interpreted alkaptonuria and other disorders as both inborn errors of metabolism and an expression of Mendelian recessive traits. Wilson disease was thought from early on to be recessively inherited from two heterozygous parents. Because of marked clinical variability within ...References1. Wilson SA. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912; 34:295-507. Google Scholar2. Critchley M. Remembering Kinnier Wilson. Mov Disord. 1988; 3:2-6. Google Scholar3. Danks DM. Disorders of copper transport. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York: McGraw-Hill; 1995:2211-35. Google Scholar4. Danks DM. Copper metabolism. In: Rimoin DL, Connor JM, Pyeritz RE, eds. Emery and Rimoin's Principles and Practice of Medical Genetics. 3d ed. New York: Churchill Livingstone; 1997:2037-46. Google Scholar5. Cumings JN. The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration. Brain. 1948; 71:410-5. Google Scholar6. Walshe JM. 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Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method. Genet Epidemiol. 1986; 3:201-9. Google Scholar13. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993; 5:327-37. Google Scholar14. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993; 5:344-50. Google Scholar15. Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chernov I, Devoto M, et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet. 1993; 5:338-43. Google Scholar16. Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995; 9:210-17. Google Scholar17. Thomas GR, Roberts EA, Walshe JM, Cox DW. Haplotypes and mutations in Wilson disease. Am J Hum Genet. 1995; 56:1315-9. Google Scholar18. McKusick VA. On-line Mendelian Inheritance in Man. 1997. Google Scholar19. Maier-Dobersberger T, Ferenci P, Polli C, Balac P, Dienes HP, Kaserer K, et al. Detection of the His1069GIn mutation in Wilson disease by rapid polymerase chain reaction. Ann Intern Med. 1997; 127:21-26. Google Scholar20. Walshe JM. Wilson's disease: yesterday, today, and tomorrow. Mov Disord. 1988; 3:10-29. Google Scholar Author, Article, and Disclosure InformationAffiliations: MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Pittsburgh, PA 15212.Grant Support: In part by grant HL 35877 from the National Institutes of Health.Corresponding Author: Reed Edwin Pyeritz, MD, PhD, Department of Human Genetics, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212-4772. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInherited Disorders of Human Copper MetabolismWilson's DiseaseInherited Disorders of Human Copper MetabolismWilson's DiseaseRapid detection of mutations in Wilson disease gene ATP7B by DNA strip technologyHepatic Copper TransportWilson diseaseWilson DiseaseHepatic copper metabolism: Insights from genetic diseaseLa maladie de Wilson. Étude clinique, thérapeutique et évolutive de 21 casHepatic transport systemsThe Wilson's disease gene and phenotypic diversityHepatocyte-specific localization and copper-dependent trafficking of the Wilson's disease protein in the liverFunctional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutationInherited Liver Disease 1 July 1997Volume 127, Issue 1Page: 70-72KeywordsAllelesGenetic diseasesLiverLiver diseasesMetabolic disordersMolecular biologyMutationPathogenesisPhenotypesPolymerase chain reaction Issue Published: 1 July 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...