title: Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea.
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.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal.
authors.forename: Maria do Carmo
authors.initials: MC
authors.lastname: Costa
authors.forename: Cristina
authors.initials: C
authors.lastname: Costa
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Silva
authors.forename: Pedro
authors.initials: P
authors.lastname: Evangelista
authors.forename: Luís
authors.initials: L
authors.lastname: Santos
authors.forename: Anabela
authors.initials: A
authors.lastname: Ferro
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Patrícia
authors.initials: P
authors.lastname: Maciel
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002819:Chorea / Q000235:genetics*; D018389:Codon, Nonsense; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D017354:Point Mutation; D011174:Portugal; D017386:Sequence Homology, Amino Acid; D013959:Thyroid Diseases / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors