Titre du document / Document title

High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa-responsive dystonia

Auteur(s) / Author(s)

STEINBERGER D. ⁽¹⁾ ; WEBER Y. ⁽¹⁾ ; KORINTHENBERG R. ⁽²⁾ ; DEUSCHL G. ⁽³⁾ ; BENECKE R. ⁽⁴⁾ ; MARTINIUS J. ⁽⁵⁾ ; MÜLLER U. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Institut für Humangenetik, Justus-Liebig-Universität, Giessen, ALLEMAGNE
⁽²⁾ Abteilung für Neuropadiatrie und Muskelerkrankungen des Universitàtskinikums, Freiburg, ALLEMAGNE
⁽³⁾ Christian-Alberts-Universität Klinik für Neurologie, Kiel, ETATS-UNIS
⁽⁴⁾ Zentrum für Nervenheilkunde, Universität Rostock, Rostock, ALLEMAGNE
⁽⁵⁾ Heckscher Klinik München, München, ALLEMAGNE

Résumé / Abstract

We performed a clinical and molecular genetic analysis in members of five families with dopa-responsive dystonia. Four mutations were detected in the gene GCH1 that codes for GTP cyclohydrolase I. Two of these mutations, a delG309 in exon 1 and a C544T transition in exon 5, have not been described before. They result in inactivation of the enzyme by truncation. The remaining two mutations, both A to G transitions, a(-2)g in intron 1 and a(-2)g in intron 2, cause truncation by abnormal splicing. The genotype of family members was correlated to their clinical phenotype (obtained before molecular analysis). Clinical symptoms observed in the families induded generalized and focal dystonia, abnormal gait, and subtle signs such as an abnormal writing test. High penetrance (0.8-1.0) was observed in four of five families if minor symptoms and signs were considered. A given mutation was more likely to cause symptoms in females than in males, thus confirming the well-established higher incidence of dopa-responsive dystonia in females than in males.

Revue / Journal Title

Annals of neurology   ISSN 0364-5134   CODEN ANNED3 

Source / Source

1998, vol. 43, n^o5, pp. 634-639 (19 ref.)

Langue / Language

Anglais

Editeur / Publisher

Willey-Liss, Hoboken, ROYAUME-UNI  (1977) (Revue)

Mots-clés anglais / English Keywords

Dystonia ; Levodopa ; Antiparkinson agent ; Clinical investigation ; Genetics ; Family study ; Exploration ; Human ; Chemotherapy ; Striated muscle disease ; Nervous system diseases ; Neurological disorder ; Involuntary movement ; Extrapyramidal syndrome ;

Mots-clés français / French Keywords

Dystonie ; Lévodopa ; Antiparkinsonien ; Exploration clinique ; Génétique ; Etude familiale ; Exploration ; Homme ; Chimiothérapie ; Muscle strié pathologie ; Système nerveux pathologie ; Trouble neurologique ; Mouvement involontaire ; Extrapyramidal syndrome ;

Mots-clés espagnols / Spanish Keywords

Distonía ; Levodopa ; Antiparkinsoniano ; Exploración clínica ; Genética ; Estudio familiar ; Exploración ; Hombre ; Quimioterapia ; Músculo estriado patología ; Sistema nervioso patología ; Trastorno neurológico ; Movimiento involuntario ; Extrapiramidal síndrome ;

Localisation / Location

INIST-CNRS, Cote INIST : 16555, 35400007555981.0110