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Further Evidence for Allelic Heterogeneity in Hartnup Disorder

Azmanov, Dimitar; Kowalczuk, Sonja; Rodgers, Helen; Auray-Blais, Christiane; Giguere, Robert; Rasko, John Edward; Broer, Stefan; Cavanaugh, Juleen

Description

Hartnup disorder is an autosomal recessive impairment of amino acid transport in kidney and intestine. Mutations in SLC6A19 have been shown to cosegregate with the disease in the predicted recessive manner; however, in two previous studies (Seow et al., Nat Genet 2004;36:1003-1007; Kleta et al., Nat Genet 2004;36:999-1002), not all causative alleles were identified in all affected individuals, raising the possibility that other genes may contribute to Hartnup disorder. We have now investigated...[Show more]

dc.contributor.authorAzmanov, Dimitar
dc.contributor.authorKowalczuk, Sonja
dc.contributor.authorRodgers, Helen
dc.contributor.authorAuray-Blais, Christiane
dc.contributor.authorGiguere, Robert
dc.contributor.authorRasko, John Edward
dc.contributor.authorBroer, Stefan
dc.contributor.authorCavanaugh, Juleen
dc.date.accessioned2015-12-08T22:23:38Z
dc.identifier.issn1059-7794
dc.identifier.urihttp://hdl.handle.net/1885/32951
dc.description.abstractHartnup disorder is an autosomal recessive impairment of amino acid transport in kidney and intestine. Mutations in SLC6A19 have been shown to cosegregate with the disease in the predicted recessive manner; however, in two previous studies (Seow et al., Nat Genet 2004;36:1003-1007; Kleta et al., Nat Genet 2004;36:999-1002), not all causative alleles were identified in all affected individuals, raising the possibility that other genes may contribute to Hartnup disorder. We have now investigated six newly acquired families of Australian and Canadian (Province of Quebec) origin and resequenced the entire coding region of SLC6A19 in families with only a single disease allele identified. We also studied one American family in whom no mutations had been identified in a previous study (Kleta et al., Nat Genet 2004;36:999-1002). We have identified seven novel mutations in SLC6A19 that show functional obliteration of the protein in vitro, explaining Hartnup disorder in all reported families so far. We demonstrate that Hartnup disorder is allelically heterogeneous with two mutated SLC6A19 alleles, whether identical or not, necessary for manifestation of the characteristic aminoaciduria in affected individuals. This study resolves the previous hypothesis that other genes contribute to the Hartnup phenotype.
dc.publisherWiley-Liss Inc
dc.sourceHuman Mutation
dc.subjectKeywords: carrier proteins and binding proteins; SLCO1A19 protein; unclassified drug; allele; aminoaciduria; article; clinical feature; controlled study; gene identification; gene mutation; gene sequence; genetic heterogeneity; Hartnup disease; human; in vitro stud Allelic heterogeneity; Aminoaciduria; Hartnup disorder; Mutation; SLC6A19
dc.titleFurther Evidence for Allelic Heterogeneity in Hartnup Disorder
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume29
dc.date.issued2008
local.identifier.absfor110311 - Medical Genetics (excl. Cancer Genetics)
local.identifier.ariespublicationu4241283xPUB97
local.type.statusPublished Version
local.contributor.affiliationAzmanov, Dimitar, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKowalczuk, Sonja, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRodgers, Helen, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAuray-Blais, Christiane, Universite de Sherbrooke
local.contributor.affiliationGiguere, Robert, Universite de Sherbrooke
local.contributor.affiliationRasko, John Edward, University of Sydney
local.contributor.affiliationBroer, Stefan, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCavanaugh, Juleen, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue10
local.bibliographicCitation.startpage1217
local.bibliographicCitation.lastpage1221
local.identifier.doi10.1002/humu.20777
dc.date.updated2015-12-08T08:54:02Z
local.identifier.scopusID2-s2.0-48749086863
local.identifier.thomsonID000260212500006
CollectionsANU Research Publications

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