PubMed:17273972 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/17273972","sourcedb":"PubMed","sourceid":"17273972","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/17273972","text":"Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions.\nDeletion 22q11.2 syndrome is the most frequent known microdeletion syndrome and is associated with a highly variable phenotype, including DiGeorge and Shprintzen (velocardiofacial) syndromes. Although haploinsufficiency of the T-box transcription factor gene TBX1 is thought to cause the phenotype, to date, only four different point mutations in TBX1 have been reported in association with six of the major features of 22q11.2 deletion syndrome. Although, for the two truncating mutations, loss of function was previously shown, the pathomechanism of the missense mutations remains unknown. We report a novel heterozygous missense mutation, H194Q, in a familial case of Shprintzen syndrome and show that this and the two previously reported missense mutations result in gain of function, possibly through stabilization of the protein dimer DNA complex. We therefore conclude that TBX1 gain-of-function mutations can result in the same phenotypic spectrum as haploinsufficiency caused by loss-of-function mutations or deletions.","tracks":[{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":107,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":174,"end":182},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":269,"end":297},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":527,"end":552},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":778,"end":797},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1020,"end":1023},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0008644"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0002254"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0008564"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0008644"},{"id":"A5","pred":"mondo_id","subj":"T3","obj":"0018923"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0018923"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0008564"},{"id":"A8","pred":"mondo_id","subj":"T7","obj":"0008644"},{"id":"A9","pred":"mondo_id","subj":"T7","obj":"0018923"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0012833"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T2","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T6","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T7","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T10","pred":"source","obj":"PMID_GLOBAL"}]},{"project":"TEST-DiseaseOrPhenotypicFeature","denotations":[{"id":"T1","span":{"begin":88,"end":105},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":107,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":269,"end":297},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":527,"end":552},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":778,"end":797},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"DISEASE"},{"id":"A2","pred":"#label","subj":"T2","obj":"D004062"},{"id":"A3","pred":"#label","subj":"T3","obj":"D004062"},{"id":"A4","pred":"#label","subj":"T4","obj":"D004062"},{"id":"A5","pred":"#label","subj":"T5","obj":"D004062"},{"subj":"T1","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T2","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T3","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T4","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T5","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"}]},{"project":"TEST-OrganismTaxon","denotations":[{"id":"T1","span":{"begin":0,"end":5},"obj":"OrganismTaxon"}],"attributes":[{"subj":"T1","pred":"source","obj":"TEST-OrganismTaxon"}]},{"project":"Test-SequenceVariant","denotations":[{"id":"T1","span":{"begin":749,"end":754},"obj":"SequenceVariant"}],"attributes":[{"subj":"T1","pred":"source","obj":"Test-SequenceVariant"}]},{"project":"Test-GeneOrGeneProduct","denotations":[{"id":"T1","span":{"begin":6,"end":10},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":334,"end":360},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":366,"end":370},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":454,"end":458},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":913,"end":941},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":988,"end":992},"obj":"GeneOrGeneProduct"}],"attributes":[{"subj":"T1","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T2","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T3","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T4","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T5","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T6","pred":"source","obj":"Test-GeneOrGeneProduct"}]},{"project":"Test-merged","denotations":[{"id":"T5","span":{"begin":778,"end":797},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":527,"end":552},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":269,"end":297},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":107,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T1","span":{"begin":88,"end":105},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T72605","span":{"begin":0,"end":5},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":988,"end":992},"obj":"GeneOrGeneProduct"},{"id":"T40572","span":{"begin":913,"end":941},"obj":"GeneOrGeneProduct"},{"id":"T41249","span":{"begin":454,"end":458},"obj":"GeneOrGeneProduct"},{"id":"T50773","span":{"begin":366,"end":370},"obj":"GeneOrGeneProduct"},{"id":"T68578","span":{"begin":334,"end":360},"obj":"GeneOrGeneProduct"},{"id":"T5046","span":{"begin":6,"end":10},"obj":"GeneOrGeneProduct"},{"id":"T32535","span":{"begin":749,"end":754},"obj":"SequenceVariant"}],"attributes":[{"id":"A4","pred":"#label","subj":"T4","obj":"D004062"},{"id":"A2","pred":"#label","subj":"T2","obj":"D004062"},{"id":"A5","pred":"#label","subj":"T5","obj":"D004062"},{"id":"A3","pred":"#label","subj":"T3","obj":"D004062"},{"id":"A1","pred":"#label","subj":"T1","obj":"DISEASE"},{"subj":"T5","pred":"source","obj":"Test-merged"},{"subj":"T4","pred":"source","obj":"Test-merged"},{"subj":"T3","pred":"source","obj":"Test-merged"},{"subj":"T2","pred":"source","obj":"Test-merged"},{"subj":"T1","pred":"source","obj":"Test-merged"},{"subj":"T72605","pred":"source","obj":"Test-merged"},{"subj":"T6","pred":"source","obj":"Test-merged"},{"subj":"T40572","pred":"source","obj":"Test-merged"},{"subj":"T41249","pred":"source","obj":"Test-merged"},{"subj":"T50773","pred":"source","obj":"Test-merged"},{"subj":"T68578","pred":"source","obj":"Test-merged"},{"subj":"T5046","pred":"source","obj":"Test-merged"},{"subj":"T32535","pred":"source","obj":"Test-merged"}]},{"project":"Test-merged-2","denotations":[{"id":"T32535","span":{"begin":749,"end":754},"obj":"SequenceVariant"},{"id":"T5046","span":{"begin":6,"end":10},"obj":"GeneOrGeneProduct"},{"id":"T68578","span":{"begin":334,"end":360},"obj":"GeneOrGeneProduct"},{"id":"T50773","span":{"begin":366,"end":370},"obj":"GeneOrGeneProduct"},{"id":"T41249","span":{"begin":454,"end":458},"obj":"GeneOrGeneProduct"},{"id":"T40572","span":{"begin":913,"end":941},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":988,"end":992},"obj":"GeneOrGeneProduct"},{"id":"T72605","span":{"begin":0,"end":5},"obj":"OrganismTaxon"},{"id":"T1","span":{"begin":88,"end":105},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":107,"end":132},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":269,"end":297},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":527,"end":552},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":778,"end":797},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"DISEASE"},{"id":"A2","pred":"#label","subj":"T2","obj":"D004062"},{"id":"A3","pred":"#label","subj":"T3","obj":"D004062"},{"id":"A4","pred":"#label","subj":"T4","obj":"D004062"},{"id":"A5","pred":"#label","subj":"T5","obj":"D004062"},{"subj":"T32535","pred":"source","obj":"Test-merged-2"},{"subj":"T5046","pred":"source","obj":"Test-merged-2"},{"subj":"T68578","pred":"source","obj":"Test-merged-2"},{"subj":"T50773","pred":"source","obj":"Test-merged-2"},{"subj":"T41249","pred":"source","obj":"Test-merged-2"},{"subj":"T40572","pred":"source","obj":"Test-merged-2"},{"subj":"T6","pred":"source","obj":"Test-merged-2"},{"subj":"T72605","pred":"source","obj":"Test-merged-2"},{"subj":"T1","pred":"source","obj":"Test-merged-2"},{"subj":"T2","pred":"source","obj":"Test-merged-2"},{"subj":"T3","pred":"source","obj":"Test-merged-2"},{"subj":"T4","pred":"source","obj":"Test-merged-2"},{"subj":"T5","pred":"source","obj":"Test-merged-2"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":106},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":107,"end":298},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":299,"end":553},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":554,"end":698},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":699,"end":960},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":961,"end":1135},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":106},"obj":"Sentence"},{"id":"T2","span":{"begin":107,"end":298},"obj":"Sentence"},{"id":"T3","span":{"begin":299,"end":553},"obj":"Sentence"},{"id":"T4","span":{"begin":554,"end":698},"obj":"Sentence"},{"id":"T5","span":{"begin":699,"end":960},"obj":"Sentence"},{"id":"T6","span":{"begin":961,"end":1135},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":366,"end":370},"obj":"gene:6899"},{"id":"T1","span":{"begin":527,"end":552},"obj":"disease:C0012236"},{"id":"T2","span":{"begin":366,"end":370},"obj":"gene:6899"},{"id":"T3","span":{"begin":527,"end":552},"obj":"disease:C0220704"},{"id":"T4","span":{"begin":454,"end":458},"obj":"gene:6899"},{"id":"T5","span":{"begin":527,"end":552},"obj":"disease:C0012236"},{"id":"T6","span":{"begin":454,"end":458},"obj":"gene:6899"},{"id":"T7","span":{"begin":527,"end":552},"obj":"disease:C0220704"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"}]},{"project":"PubCasesORDO","denotations":[{"id":"AB1","span":{"begin":270,"end":297},"obj":"ORDO:567"},{"id":"AB2","span":{"begin":778,"end":797},"obj":"ORDO:567"}],"namespaces":[{"prefix":"ORDO","uri":"http://www.orpha.net/ORDO/Orphanet_"}],"attributes":[{"subj":"AB1","pred":"source","obj":"PubCasesORDO"},{"subj":"AB2","pred":"source","obj":"PubCasesORDO"}]},{"project":"tmVarCorpus","denotations":[{"id":"T1","span":{"begin":749,"end":754},"obj":"ProteinMutation:p|SUB|H|194|Q"}],"attributes":[{"subj":"T1","pred":"source","obj":"tmVarCorpus"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PMID_GLOBAL","color":"#eca093","default":true},{"id":"TEST-DiseaseOrPhenotypicFeature","color":"#939fec"},{"id":"TEST-OrganismTaxon","color":"#b9ec93"},{"id":"Test-SequenceVariant","color":"#ec93d3"},{"id":"Test-GeneOrGeneProduct","color":"#93eceb"},{"id":"Test-merged","color":"#ecd093"},{"id":"Test-merged-2","color":"#b693ec"},{"id":"sentences","color":"#93ec9c"},{"id":"DisGeNET","color":"#ec93a3"},{"id":"PubCasesORDO","color":"#93bdec"},{"id":"tmVarCorpus","color":"#d7ec93"}]}]}}