{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:45:34Z","timestamp":1770349534998,"version":"3.49.0"},"reference-count":26,"publisher":"BMJ","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Heart"],"accepted":{"date-parts":[[2010,6,30]]},"published-print":{"date-parts":[[2010,10,15]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor <jats:italic>TBX1<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess the contribution of common and rare <jats:italic>TBX1<\/jats:italic> genetic variants to TOF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Rare <jats:italic>TBX1<\/jats:italic> variants were sought by resequencing coding exons and splice-site boundaries. Common <jats:italic>TBX1<\/jats:italic> variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study demonstrates that rare <jats:italic>TBX1<\/jats:italic> variants with functional consequences are present in a small proportion of non-syndromic TOF.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/hrt.2010.200121","type":"journal-article","created":{"date-parts":[[2010,10,11]],"date-time":"2010-10-11T11:44:19Z","timestamp":1286797459000},"page":"1651-1655","source":"Crossref","is-referenced-by-count":67,"title":["Systematic survey of variants in <i>TBX1<\/i> in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common 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