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.
Breedveld
Guido J
GJ
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
van Dongen
Jeroen W F
JW
Danesino
Cesare
C
Guala
Andrea
A
Percy
Alan K
AK
Dure
Leon S
LS
Harper
Peter
P
Lazarou
Lazarus P
LP
van der Linde
Herma
H
Joosse
Marijke
M
Grüters
Annette
A
MacDonald
Marcy E
ME
de Vries
Bert B A
BB
Arts
Willem Frans M
WF
Oostra
Ben A
BA
Krude
Heiko
H
Heutink
Peter
P
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
D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors