Mutations in TITF-1 are associated with benign hereditary chorea
Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC.
|*Mutation, Amino Acid Sequence, Choreatic Disorders/*genetics, Female, Haplotypes, Humans, In Situ Hybridization, Fluorescence, Male, Molecular Sequence Data, Nuclear Proteins/*genetics/metabolism, Pedigree, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Sequence Alignment, Sequence Analysis, DNA, Transcription Factors/*genetics/metabolism|
|Human Molecular Genetics|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Breedveld, G.J, Guala, A, Oostra, B.A, Percy, A.K, Dure, L.S, Harper, P, … Heutink, P. (2002). Mutations in TITF-1 are associated with benign hereditary chorea. Human Molecular Genetics. Retrieved from http://hdl.handle.net/1765/9889