title: Mutations in TITF-1 are associated with benign hereditary chorea.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Breedveld
authors.forename: Jeroen W F
authors.initials: JW
authors.lastname: van Dongen
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Andrea
authors.initials: A
authors.lastname: Guala
authors.forename: Alan K
authors.initials: AK
authors.lastname: Percy
authors.forename: Leon S
authors.initials: LS
authors.lastname: Dure
authors.forename: Peter
authors.initials: P
authors.lastname: Harper
authors.forename: Lazarus P
authors.initials: LP
authors.lastname: Lazarou
authors.forename: Herma
authors.initials: H
authors.lastname: van der Linde
authors.forename: Marijke
authors.initials: M
authors.lastname: Joosse
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Willem Frans M
authors.initials: WF
authors.lastname: Arts
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
mesh_terms: D000595:Amino Acid Sequence; D002819:Chorea / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors