Mutations in TITF-1 are associated with benign hereditary chorea
January 2002
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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.
- Male
- Female
- Humans
- Research Support, Non-U.S. Gov't
- *Mutation
- Amino Acid Sequence
- Molecular Sequence Data
- Sequence Alignment
- Research Support, U.S. Gov't, P.H.S.
- In Situ Hybridization, Fluorescence
- Pedigree
- Sequence Analysis, DNA
- Nuclear Proteins/*genetics/metabolism
- Transcription Factors/*genetics/metabolism
- Choreatic Disorders/*genetics
- Haplotypes
- family
- chromosome
- deletion
- mutation
- sequence
- chorea
- protein
- thyroid
- marker
- region
- genomic
- 200 control chromosomes
- factor
- disorder
- genetic
- analysis
- family uk 1
- chromosome 14 q
- chromosome 14
- transcription
