title: Myoclonus-dystonia syndrome due to tyrosine hydroxylase deficiency.
abstract: OBJECTIVE
  To present a new family with tyrosine hydroxylase deficiency (THD) that presented with a new phenotype of predominant, levodopa-responsive myoclonus with dystonia due to compound heterozygosity of one previously reported mutation in the promoter region and a novel nonsynonymous mutation in the other allele, thus expanding the clinical and genetic spectrum of this disorder.
  
  
  METHODS
  We performed detailed clinical examination of the family and electrophysiology to characterize the myoclonus. We performed analysis of the TH gene and in silico prediction of the possible effect of nonsynonymous substitutions on protein structure.
  
  
  RESULTS
  Electrophysiology suggested that the myoclonus was of subcortical origin. Genetic analysis of the TH gene revealed compound heterozygosity of a point mutation in the promoter region (c.1-71 C>T) and a novel nonsynonymous substitution in exon 12 (c.1282G>A, p.Gly428Arg). The latter is a novel variant, predicted to have a deleterious effect on the TH protein function and is the first pathogenic TH mutation in patients of African ancestry.
  
  
  CONCLUSIONS
  We presented a THD family with predominant myoclonus-dystonia and a new genotype. It is important to consider THD in the differential diagnosis of myoclonus-dystonia, because early treatment with levodopa is crucial for these patients.
authors: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. m.stamelou@ucl.ac.uk
authors: Maria
authors: M
authors: Stamelou
authors: Niccolo E
authors: NE
authors: Mencacci
authors: Carla
authors: C
authors: Cordivari
authors: Amit
authors: A
authors: Batla
authors: Nick W
authors: NW
authors: Wood
authors: Henry
authors: H
authors: Houlden
authors: John
authors: J
authors: Hardy
authors: Kailash P
authors: KP
authors: Bhatia
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D020821:Dystonic Disorders / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D004569:Electroencephalography; D004576:Electromyography; D005073:Evoked Potentials, Somatosensory / Q000235:genetics; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics; D012018:Reflex / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency* / Q000235:genetics*; D055815:Young Adult
chemical_list: D014446:Tyrosine 3-Monooxygenase