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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
CREB-Binding Protein
-
Cell Movement
-
DAX-1 Orphan Nuclear Receptor
-
DNA-Binding Proteins / genetics
-
Disease*
-
Eye Proteins
-
Helix-Loop-Helix Motifs
-
High Mobility Group Proteins / genetics
-
Homeodomain Proteins / genetics
-
Humans
-
Intellectual Disability / genetics
-
Kruppel-Like Transcription Factors
-
Microphthalmia-Associated Transcription Factor
-
Mutation
-
Nerve Tissue Proteins / genetics
-
Nuclear Proteins / genetics
-
PAX2 Transcription Factor
-
PAX3 Transcription Factor
-
PAX6 Transcription Factor
-
POU Domain Factors
-
Paired Box Transcription Factors
-
Receptors, Androgen / genetics
-
Receptors, Calcitriol / genetics
-
Receptors, Estrogen / genetics
-
Receptors, Retinoic Acid / genetics
-
Receptors, Thyroid Hormone / genetics
-
Repressor Proteins*
-
Rubinstein-Taybi Syndrome / genetics
-
SOX9 Transcription Factor
-
Sex-Determining Region Y Protein
-
Trans-Activators*
-
Transcription Factor Pit-1
-
Transcription Factors / genetics*
-
WT1 Proteins
-
Xenopus Proteins*
-
Zinc Finger Protein Gli3
-
Zinc Fingers
-
alpha-Thalassemia / genetics
-
von Hippel-Lindau Disease / genetics
Substances
-
DAX-1 Orphan Nuclear Receptor
-
DNA-Binding Proteins
-
Eye Proteins
-
GLI3 protein, Xenopus
-
GLI3 protein, human
-
Gli3 protein, mouse
-
High Mobility Group Proteins
-
Homeodomain Proteins
-
Kruppel-Like Transcription Factors
-
MITF protein, human
-
MSX2 protein
-
Microphthalmia-Associated Transcription Factor
-
NR0B1 protein, human
-
Nerve Tissue Proteins
-
Nr0b1 protein, mouse
-
Nuclear Proteins
-
PAX2 Transcription Factor
-
PAX2 protein, human
-
PAX3 Transcription Factor
-
PAX3 protein, human
-
PAX6 Transcription Factor
-
PAX6 protein, human
-
POU Domain Factors
-
POU1F1 protein, human
-
POU3F4 protein, human
-
Paired Box Transcription Factors
-
Pax3 protein, Xenopus
-
Pax6 protein, mouse
-
Receptors, Androgen
-
Receptors, Calcitriol
-
Receptors, Estrogen
-
Receptors, Retinoic Acid
-
Receptors, Thyroid Hormone
-
Repressor Proteins
-
SOX9 Transcription Factor
-
SOX9 protein, human
-
Sex-Determining Region Y Protein
-
Sox9 protein, mouse
-
Trans-Activators
-
Transcription Factor Pit-1
-
Transcription Factors
-
WT1 Proteins
-
Xenopus Proteins
-
Zinc Finger Protein Gli3
-
empty spiracles homeobox proteins
-
Pax3 protein, mouse
-
Pou3f4 protein, mouse
-
CREB-Binding Protein
-
CREBBP protein, human