Mutations in TITF-1 are associated with benign hereditary chorea

Guido J. Breedveld, Jeroen W F Van Dongen, Cesare Danesino, Andrea Guala, Alan K. Percy, Leon S. Dure, Peter Harper, Lazarus P. Lazarou, Herma Van Der Linde, Marijke Joosse, Annette Grüters, Marcy E. MacDonald, Bert B A De Vries, Willem Frans M Arts, Ben A. Oostra, Heiko Krude, Peter Heutink

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalHuman Molecular Genetics
Volume11
Issue number8
Publication statusPublished - Apr 15 2002

ASJC Scopus subject areas

  • Genetics

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    Breedveld, G. J., Van Dongen, J. W. F., Danesino, C., Guala, A., Percy, A. K., Dure, L. S., Harper, P., Lazarou, L. P., Van Der Linde, H., Joosse, M., Grüters, A., MacDonald, M. E., De Vries, B. B. A., Arts, W. F. M., Oostra, B. A., Krude, H., & Heutink, P. (2002). Mutations in TITF-1 are associated with benign hereditary chorea. Human Molecular Genetics, 11(8), 971-979.