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Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea

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Abstract

Benign hereditary chorea (BHC) is an autosomaldominant disorder of early onset characterized by a slowly progressing or nonprogressing chorea, without cognitive decline or other progressive neurologic dysfunction, but also by the existence of heterogeneity of the clinical presentation within and among families. The genetic cause of BHC is the presence of either point mutations or deletions in the thyroid transcription factor 1 gene (TITF1). We studied a Portuguese BHC family composed of two probands: a mother and her only son. The patients were identified in a neurology out-patient clinic showing mainly involuntary choreiform movements since childhood, myoclonic jerks, falls, and dysarthria. We performed magnetic resonance imaging (MRI), electroencephalogram (EEG), nerve conduction studies, thyroid ultrasound scan, biochemical thyroid tests, and electrocardiogram (ECG). We excluded Huntington disease by appropriate genetic testing and sequenced the entire TITF1 gene for both patients. The patients showed MRI alterations: (1) in the mother, abnormal hyperintense pallida and cortical cerebral/cerebellar atrophy; and (2) in the son, small hyperintense foci in the cerebellum and subtle enlargement of the fourth ventricle. Sequence analysis of the TITF1 gene in these patients revealed the presence of a heterozygous C > T substitution at nucleotide 745, leading to the replacement of a glutamine at position 249 for a premature stop codon. A previously undescribed nonsense mutation in the TITF1 gene was identified as being the genetic cause of BHC in this family.

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Acknowledgements

We would like to thank the patients and family members for their collaboration and Drs. Peter Heutink and Heiko Krude for useful discussion. M.C.C. and A.F. are the recipients of Ph.D. scholarships from Fundação para a Ciência e Tecnologia, MCT, Portugal (SFRH/BD/9759/2003 and SFRH/BD/1288/2000, respectively).

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Authors and Affiliations

  1. Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal

    Maria do Carmo Costa & Patrícia Maciel

  2. Neurology Department, Hospital Fernando Fonseca, Amadora, Portugal

    Cristina Costa

  3. Rehabilitation Department, Hospital Fernando Fonseca, Amadora, Portugal

    Ana Paula Silva

  4. Neuroimaging Department, Hospital Fernando Fonseca, Amadora, Portugal

    Pedro Evangelista

  5. Neurology Department, Hospital Egas Moniz, Lisbon, Portugal

    Luís Santos

  6. UnIGENe, IBMC, University of Porto, Porto, Portugal

    Anabela Ferro & Jorge Sequeiros

  7. Department of Population Genetics, ICBAS, University of Porto, Porto, Portugal

    Jorge Sequeiros

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  1. Maria do Carmo Costa
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  2. Cristina Costa
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  3. Ana Paula Silva
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  4. Pedro Evangelista
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  5. Luís Santos
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  8. Patrícia Maciel
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Correspondence to Patrícia Maciel.

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do Carmo Costa, M., Costa, C., Silva, A. et al. Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea. Neurogenetics 6, 209–215 (2005). https://doi.org/10.1007/s10048-005-0013-1

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  • DOI: https://doi.org/10.1007/s10048-005-0013-1

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