Novel missense mutations in the XXXX gene alter transcriptional activity.

@entity1 @entity3329 @entity66 @entity21951 @entity19 @entity4269 @entity1373 @entity1887 @entity4096 @entity8944 @entity17967
Mutations in the @entity8944 gene that codes for a forkhead transcription factor are associated with primary @entity4269 that usually develops around puberty. @entity66 include @entity21951 and, very frequently, superficial and deep @entity4096 . Most mutations reported so far either truncate the protein or are missense mutations in the forkhead domain causing a loss of function. The haplo-insufficient state is associated with @entity1373 in @entity19 as well as in @entity1 . We analyzed the @entity8944 gene in 288 @entity1 with primary @entity4269 and found 11 pathogenic mutations, of which 9 are novel. Of those, 5 were novel missense mutations of which 4 were located outside of the forkhead domain. To examine their pathogenic potential we performed a transactivation assay using a luciferase reporter construct driven by @entity17967 response elements. We found that the mutations outside the forkhead domain cause a gain of function as measured by luciferase activity. @entity1 characteristics conform to previous reports with the exception of @entity21951 , which was found in only 2 @entity1 out of 11. @entity8944 mutations causing @entity21951 reported thus far result in @entity1887 and lead to @entity1373 . Our results suggest that gain-of-function mutations may also cause @entity4269 . One would expect that in this case, @entity3329 would be the underlying abnormality. @entity1 with activating mutations might present with Meige disease.
