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Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: Association with liver disease

Show simple item record Barada K. El-Atrache M. El-Hajj I.I. Rida K. El-Hajjar J. Mahfoud Z. Usta J.
dc.contributor.editor Jul-2010 2017-10-05T15:37:49Z 2017-10-05T15:37:49Z 2010
dc.identifier 10.1097/MCG.0b013e3181ce5138
dc.identifier.issn 01920790
dc.description.abstract Objective: To determine whether any correlation exists between the phenotype and genotype of 2 Lebanese families with members affected with Wilson disease (WD). Background: WD is an autosomal-recessive disorder of copper transport with significant phenotypic diversity. Most patients are compound heterozygous making it difficult to establish a clear link between phenotype and genotype. Study: We investigated 14 members from 2 Lebanese families (H and Z) with 5 members affected with WD. Mutation analysis of the ATP7B gene, and clinical assessments were carried out for both families. We also performed a literature search retrieving reported phenotypes of all patients homozygous to mutations in any of the 21 exons of the ATP7B. Results: Patients of the H and Z-families were found homozygous for the respective Asn1270Ser and Pro1273Leu mutations in the adenosine triphosphate (ATP) hinge region of exon 18. Of the healthy members, 6 were heterozygous and 3 had normal sequences. Clinically, 4 patients had liver cirrhosis and 1 had asymptomatic transaminitis. One of the patients also had neurologic symptoms. Screening the literature for patients homozygous for mutations in the ATP hinge region identified 25 patients including ours. The overall prevalence of the hepatic phenotype among patients homozygous for mutation in exon 18 was 80percent and was significantly higher than those in exons 7, 14, and 21. Conclusions: We hereby report the association of liver disease with homozygous mutations in the conserved ATP hinge region of exon 18 of the ATP7B gene. Copyright © 2010 by Lippincott Williams and Wilkins.
dc.format.extent Pages: (432-439)
dc.language English
dc.publisher PHILADELPHIA
dc.relation.ispartof Publication Name: Journal of Clinical Gastroenterology; Publication Year: 2010; Volume: 44; no. 6; Pages: (432-439);
dc.source Scopus
dc.title Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: Association with liver disease
dc.type Article
dc.contributor.affiliation Barada, K., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, United States
dc.contributor.affiliation El-Atrache, M., Faculty of Medicine, American University of Beirut, France
dc.contributor.affiliation El-Hajj, I.I., Faculty of Medicine, American University of Beirut, France
dc.contributor.affiliation Rida, K., Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation El-Hajjar, J., Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Mahfoud, Z., Department of Epidemiology and Population Health, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Usta, J., Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.authorAddress Usta, J.; Department of Biochemistry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Internal Medicine; Division: Gastroenterology and Hepatology;
dc.contributor.authorDepartment Internal Medicine
dc.contributor.authorDivision Gastroenterology and Hepatology
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Barada, K
dc.contributor.authorInitials El-Atrache, M
dc.contributor.authorInitials El-Hajj, II
dc.contributor.authorInitials Rida, K
dc.contributor.authorInitials El-Hajjar, J
dc.contributor.authorInitials Mahfoud, Z
dc.contributor.authorInitials Usta, J
dc.contributor.authorReprintAddress Usta, J (reprint author), Amer Univ Beirut, Fac Med, Dept Biochem, Beirut, Lebanon.
dc.contributor.authorUniversity American University of Beirut Medical Center
dc.description.cited Abdelghaffar TY, 2008, J HUM GENET, V53, P681, DOI 10.1007-s10038-008-0298-7; Ala A, 2005, HEPATOLOGY, V41, P668, DOI 10.1002-hep.20601; Barada K, 2007, CLIN GENET, V72, P264, DOI 10.1111-j.1399-0004.2007.00853.x; Brage A, 2007, HEPATOL RES, V37, P18; BULL PC, 1994, NAT GENET, V6, P214; Butler P, 2001, MOL GENET METAB, V72, P223, DOI 10.1006-mgme.2000.3143; Caca K, 2001, J HEPATOL, V35, P575, DOI 10.1016-S0168-8278(01)00219-7; CAPRAI S, 2005, J PEDIAT, V148, P138; Curtis D, 1999, HUM MUTAT, V14, P304, DOI 10.1002-(SICI)1098-1004(199910)14:4304::AID-HUMU53.0.CO;2-W; Czlonkowska A, 2009, MOVEMENT DISORD, V24, P1066, DOI 10.1002-mds.22474; Dedoussis GVZ, 2005, ANN HUM GENET, V69, P268, DOI 10.1046-j.1529-8817.2005.00171.x; Deguti MM, 2004, HUM MUTAT, V23, P398, DOI 10.1002-humu.9227; Ferenci P, 2003, LIVER INT, V23, P139, DOI 10.1034-j.1600-0676.2003.00824.x; Ferenci P, 2007, GASTROENTEROLOGY, V132, P1294, DOI 10.1053-j.gastro.2007.02.057; Ferenci P, 2006, HUM GENET, V120, P151, DOI 10.1007-s00439-006-0202-5; Firneisz G, 2002, AM J MED GENET, V108, P23, DOI 10.1002-ajmg.10220; Folhoffer A, 2007, EUR J GASTROEN HEPAT, V19, P105, DOI 10.1097-01.meg.0000223904.70492.0b; Garcia-Villarreal L, 2000, HEPATOLOGY, V32, P1329, DOI 10.1053-jhep.2000.20152; Gromadzka G, 2005, CLIN GENET, V68, P524, DOI 10.1111-j.1399-0004.2005.00528.x; Gu YH, 2003, CLIN GENET, V64, P479, DOI 10.1046-j.1399-0004.2003.00179.x; Gupta A, 2005, HUM GENET, V118, P49, DOI 10.1007-s00439-005-0007-y; HAO DH, 1998, EUR J HUM GENET, V6, P616; Huffman DL, 2001, ANNU REV BIOCHEM, V70, P677, DOI 10.1146-annurev.biochem.70.1.677; Huster D, 2003, GASTROENTEROLOGY, V124, P335, DOI 10.1053-gast.2003.50066; Kalinsky H, 1998, HUM MUTAT, V11, P145, DOI 10.1002-(SICI)1098-1004(1998)11:2145::AID-HUMU73.0.CO;2-I; Kucinskas L, 2008, WORLD J GASTROENTERO, V14, P5876, DOI 10.3748-wjg.14.5876; Kumar S, 2005, CLIN GENET, V67, P443, DOI 10.1111-j.1399-0004.2005.00440.x; Kusuda Y, 2000, J HUM GENET, V45, P86, DOI 10.1007-s100380050017; Leggio L, 2007, DIGEST DIS SCI, V52, P2570, DOI 10.1007-s10620-006-9666-3; Leggio L, 2006, DIGEST DIS SCI, V51, P34, DOI 10.1007-s10620-006-3080-8; Leggio L, 2007, LANCET, V369, P902, DOI 10.1016-S0140-6736(07)60437-1; Liu XQ, 2004, WORLD J GASTROENTERO, V10, P590; Loudianos G, 1999, HUM MUTAT, V14, P294, DOI 10.1002-(SICI)1098-1004(199910)14:4294::AID-HUMU43.0.CO;2-9; Loudianos G, 1999, J MED GENET, V36, P833; Loudianos G, 2003, GENET TEST, V7, P107, DOI 10.1089-109065703322146786; Loudianos G, 2000, SEMIN LIVER DIS, V20, P353, DOI 10.1055-s-2000-9389; Luza Sandra C., 1996, American Journal of Clinical Nutrition, V63, p812S; Machado AAC, 2008, PARKINSONISM RELAT D, V14, P246, DOI 10.1016-j.parkreldis.2007.08.002; Majumdar R, 2000, J NEUROL SCI, V179, P140, DOI 10.1016-S0022-510X(00)00399-3; Margarit E, 2005, Hum Genet, V118, P544; Margarit E, 2005, CLIN GENET, V68, P61, DOI 10.1111-j.1399-0004.2005.00439.x; Obrador BD, 2006, EUR J GASTROEN HEPAT, V18, P57, DOI 10.1097-00042737-200601000-00010; Okada T, 2000, HUM MUTAT, V15, P454, DOI 10.1002-(SICI)1098-1004(200005)15:5454::AID-HUMU73.0.CO;2-J; Panagiotakaki E, 2004, AM J MED GENET A, V131A, P168, DOI 10.1002-ajmg.a.30345; Pendlebury ST, 2004, NEUROLOGY, V63, P1982; PETRUKHIN K, 1994, HUM MOL GENET, V3, P1647, DOI 10.1093-hmg-3.9.1647; Pinzani M, 2005, J HEPATOL, V42, pS22, DOI 10.1016-j.jhep.2004.12.008; Prohaska JR, 2004, J NUTR, V134, P1003; Riordan SM, 2001, J HEPATOL, V34, P165, DOI 10.1016-S0168-8278(00)00028-3; Rosenzweig AC, 2002, CHEM BIOL, V9, P673, DOI 10.1016-S1074-5521(02)00156-4; Santhosh S, 2008, WORLD J GASTROENTERO, V14, P4672, DOI 10.3748-wjg.14.4672; Santhosh S, 2006, Indian J Gastroenterol, V25, P277; Shah AB, 1997, AM J HUM GENET, V61, P317, DOI 10.1086-514864; SHIMIZU N, 1995, BIOCHEM BIOPH RES CO, V217, P16, DOI 10.1006-bbrc.1995.2739; Shimizu N, 1999, PEDIATR INT, V41, P409, DOI 10.1046-j.1442-200x.1999.01092.x; Stapelbroek JM, 2004, J HEPATOL, V41, P758, DOI 10.1016-j.jhep.2004.07.017; Takeshita Y, 2002, J HUM GENET, V47, P543, DOI 10.1007-s100380200082; Taly AB, 2007, MEDICINE, V86, P112, DOI 10.1097-MD.0b013e318045a00e; TANZI RE, 1993, NAT GENET, V5, P344, DOI 10.1038-ng1293-344; Terada K, 1998, INT J BIOCHEM CELL B, V30, P1063, DOI 10.1016-S1357-2725(98)00073-9; THOMAS GR, 1995, AM J HUM GENET, V56, P1140; THOMAS GR, 1995, NAT GENET, V9, P451; *U ALB DEP MED GEN, WILS DIS MUT DAT; Velez-Pardo C, 2004, NEUROSCI LETT, V367, P360, DOI 10.1016-j.neulet.2004.06.032; Vrabelova S, 2005, MOL GENET METAB, V86, P277, DOI 10.1016-j.ymgme.2005.05.004; Waldenstrom E, 1996, GENOMICS, V37, P303, DOI 10.1006-geno.1996.0564; WU Y, 2001, ARCH NEUROL-CHICAGO, V58, P971; Yoo HW, 2002, GENET MED, V4, p43S, DOI 10.1097-01.GIM.0000040260.30727.EB
dc.description.citedCount 9
dc.description.citedTotWOSCount 11
dc.description.citedWOSCount 10
dc.format.extentCount 8
dc.identifier.coden JCGAD
dc.identifier.pubmedID 20485189
dc.identifier.scopusID 77953809282
dc.publisher.address 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
dc.relation.ispartOfISOAbbr J. Clin. Gastroenterol.
dc.relation.ispartOfIssue 6
dc.relation.ispartofPubTitle Journal of Clinical Gastroenterology
dc.relation.ispartofPubTitleAbbr J. Clin. Gastroenterol.
dc.relation.ispartOfVolume 44
dc.source.ID WOS:000278817000010
dc.type.publication Journal
dc.subject.otherAuthKeyword ATP hinge
dc.subject.otherAuthKeyword ATP7B
dc.subject.otherAuthKeyword copper toxicity
dc.subject.otherAuthKeyword liver disease
dc.subject.otherAuthKeyword Wilson disease
dc.subject.otherChemCAS Adenosine Triphosphatases, 3.6.1.-
dc.subject.otherChemCAS Adenosine Triphosphate, 56-65-5
dc.subject.otherChemCAS Cation Transport Proteins
dc.subject.otherChemCAS Wilson disease protein,
dc.subject.otherIndex adolescent
dc.subject.otherIndex adult
dc.subject.otherIndex article
dc.subject.otherIndex ATP7B gene
dc.subject.otherIndex autosomal recessive disorder
dc.subject.otherIndex child
dc.subject.otherIndex clinical article
dc.subject.otherIndex disease association
dc.subject.otherIndex gene
dc.subject.otherIndex gene mutation
dc.subject.otherIndex genotype phenotype correlation
dc.subject.otherIndex human
dc.subject.otherIndex hypertransaminasemia
dc.subject.otherIndex Lebanon
dc.subject.otherIndex liver cirrhosis
dc.subject.otherIndex liver disease
dc.subject.otherIndex neurologic disease
dc.subject.otherIndex priority journal
dc.subject.otherIndex Wilson disease
dc.subject.otherIndex Adenosine Triphosphatases
dc.subject.otherIndex Adenosine Triphosphate
dc.subject.otherIndex Adolescent
dc.subject.otherIndex Cation Transport Proteins
dc.subject.otherIndex Child
dc.subject.otherIndex Exons
dc.subject.otherIndex Family
dc.subject.otherIndex Female
dc.subject.otherIndex Genotype
dc.subject.otherIndex Hepatolenticular Degeneration
dc.subject.otherIndex Homozygote
dc.subject.otherIndex Humans
dc.subject.otherIndex Lebanon
dc.subject.otherIndex Liver Diseases
dc.subject.otherIndex Male
dc.subject.otherIndex Mutation
dc.subject.otherIndex Pedigree
dc.subject.otherIndex Phenotype
dc.subject.otherIndex Sequence Analysis, DNA
dc.subject.otherKeywordPlus COPPER-TRANSPORTING ATPASE
dc.subject.otherKeywordPlus MOLECULAR CHARACTERIZATION
dc.subject.otherKeywordPlus JAPANESE PATIENTS
dc.subject.otherKeywordPlus HIGH PREVALENCE
dc.subject.otherKeywordPlus COMMON MUTATIONS
dc.subject.otherKeywordPlus H1069Q MUTATION
dc.subject.otherKeywordPlus DIAGNOSIS
dc.subject.otherKeywordPlus IDENTIFICATION
dc.subject.otherKeywordPlus POPULATION
dc.subject.otherWOS Gastroenterology and Hepatology

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