title: Transcription factors in disease.
abstract: Mutations affecting several predominantly tissue-specific transcriptional regulators have recently been associated with disease phenotypes. Although the mutational spectrum is variable, many of the reported cases involve clear loss-of-function mutations-such as Waardenburg syndrome type 1, aniridia and Rubinstein-Taybi syndrome-suggesting that the genetic mechanism involved in disease is haplo-insufficiency. The high degree of dosage sensitivity often appears to affect only a subset of the tissues that express the gene. Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. dieter@hgu.mrc.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Engelkamp
authors.forename: V
authors.initials: V
authors.lastname: van Heyningen
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein; D002465:Cell Movement; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics; D004194:Disease; D005136:Eye Proteins; D018257:Helix-Loop-Helix Motifs; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D051762:PAX2 Transcription Factor; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D050809:POU Domain Factors; D051761:Paired Box Transcription Factors; D011944:Receptors, Androgen / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D012097:Repressor Proteins; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*; D025721:WT1 Proteins; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3; D016335:Zinc Fingers; D017085:alpha-Thalassemia / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D050882:CREB-Binding Protein; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D051739:Microphthalmia-Associated Transcription Factor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D050809:POU Domain Factors; D051761:Paired Box Transcription Factors; D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D025721:WT1 Proteins; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3; D000099260:Empty Spiracles Homeobox Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; C497234:MITF protein, human; C084119:MSX2 protein; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; C497318:PAX2 protein, human; C489409:PAX3 protein, human; C000605730:PAX6 protein, human; C494187:POU1F1 protein, human; C091774:POU3F4 protein, human; C489411:Pax3 protein, Xenopus; C000605732:Pax6 protein, mouse; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; C068686:Pax3 protein, mouse; C074067:Pou3f4 protein, mouse; C494363:CREBBP protein, human