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dc.contributor.authorTeraoka, SN
dc.contributor.authorTelatar, M
dc.contributor.authorBecker-Catania, S
dc.contributor.authorLiang, T
dc.contributor.authorOnengut, S
dc.contributor.authorTolun, A
dc.contributor.authorChessa, L
dc.contributor.authorSanal, O
dc.contributor.authorBernatowska, E
dc.contributor.authorGatti, RA
dc.contributor.authorConcannon, P
dc.date.accessioned2019-12-10T11:33:09Z
dc.date.available2019-12-10T11:33:09Z
dc.date.issued1999
dc.identifier.issn0002-9297
dc.identifier.urihttps://doi.org/10.1086/302418
dc.identifier.urihttp://hdl.handle.net/11655/16088
dc.description.abstractMutations resulting in defective splicing constitute a significant proportion (30/62 [48%]) of a new series of mutations in the ATM gene in patients with ataxia-telangiectasia (AT) that were detected by the protein-truncation assay followed by sequence analysis of genomic DNA. Fewer than half of the splicing mutations involved the canonical AG splice-acceptor site or GT splice-donor site. A higher percentage of mutations occurred at less stringently conserved sites, including silent mutations of the last nucleotide of exons, mutations in nucleotides other than the conserved AG and GT in the consensus splice sites, and creation of splice-acceptor or splice-donor sites in either introns or exons. These splicing mutations led to a variety of consequences, including exon skipping and, to a lesser degree, intron retention, activation of cryptic splice sites, or creation of new splice sites. In addition, 5 of 12 nonsense mutations and 1 missense mutation were associated with deletion in the cDNA of the exons in which the mutations occurred. No ATM protein was detected by western blotting in any AT cell line in which splicing mutations were identified. Several cases of exon skipping in both normal controls and patients for whom no underlying defect could be found in genomic DNA were also observed, suggesting caution in the interpretation of exon deletions observed in ATM cDNA when there is no accompanying identification of genomic mutations.
dc.language.isoen
dc.publisherCell Press
dc.relation.isversionof10.1086/302418
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGenetics & Heredity
dc.titleSplicing Defects In The Ataxia-Telangiectasia Gene, Atm: Underlying Mutations And Consequences
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalAmerican Journal Of Human Genetics
dc.contributor.departmentTıbbi Genetik
dc.identifier.volume64
dc.identifier.issue6
dc.identifier.startpage1617
dc.identifier.endpage1631
dc.description.indexWoS
dc.description.indexScopus


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