Mutations in TAZ/WWTR1, a co-activator of NKX2.1 and PAX8 are not a frequent cause of thyroid dysgenesis.
OBJECTIVE
In 80-85% of cases, congenital hypothyroidism is associated with thyroid dysgenesis (TD), but only in a small percentage of cases mutations in thyroid transcription factors (NKX2.1, PAX8, FOXE1, and NKX2.5) have been associated with the disease. Several studies demonstrated that the activity of the transcription factors can be modulated by the interaction with other proteins, such as coactivators and co-repressors, and TAZ (transcriptional co-activator with PDZ-binding motif or WWTR1) is a co-activator interacting with both NKX2.1 and PAX8. In the present study we investigate the role of TAZ in the pathogenesis of TD.


METHODS
By Single Stranded Conformational Polymorphism, we screened the entire TAZ coding sequence for mutations in 96 patients with TD and in 96 normal controls.


RESULTS
No mutations were found in patients and controls, but we found several polymorphisms in both groups. No significant differences could be demonstrated in the prevalence of the mutations between patients and controls.


CONCLUSIONS
Our data indicate that TAZ mutations are not a cause of TD in the series of patients studied.
Ferrara
A M
AM
Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy.
De Sanctis
L
L
Rossi
G
G
Capuano
S
S
Del Prete
G
G
Zampella
E
E
Gianino
P
P
Corrias
A
A
Fenzi
G
G
Zannini
M
M
Macchia
P E
PE
D000217:Acyltransferases; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D050033:Thyroid Dysgenesis / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human