Wide expressivity variation and high but no gender-related penetrance in two dopa-responsive dystonia families with a novel GCH-I mutation

Movement Disorders : Official Journal of the Movement Disorder Society
Antonino UnciniDomenico Gambi

Abstract

We describe the clinical and molecular correlates in two Italian families with dopa-responsive dystonia (DRD) and the same novel mutation of GTP-cyclohydrolase I (GCH-I) gene. Thirty-five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is present in 7 subjects currently under the age of 40. In 1 patient bilateral foot dystonia was evident at birth suggesting that dystonia may be active as early as in utero. In another patient, dystonia spontaneously remitted in adolescence, to relapse 8 years later, as writer's cramp. Dystonia and parkinsonian signs are present in 5 other patients. In 2 subjects an isolated parkinsonism started over the age of 45. A 5-base pair insertion at codon 242 within exon 6 of GTP-cyclohydrolase I (GCH-I) gene that shifts the reading frame and results in a premature stop at codon 247 with truncation of the polypeptide has been detected in 21 subjects. Considering dystonia and parkinsonism the overall penetrance is 0.71 and not significantly different in men (0.69) and women (0.75). Genealogical studies seem to exclude that these families are related but haplotype analysis suggests a single founder. Our findings in subjects with the same mutation indicate a w...Continue Reading

References

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Citations

Mar 1, 2012·Journal of Neural Transmission·Tufan NaiyaJharna Ray
Jul 16, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·E Fernández-Alvarez
Jun 3, 2008·Experimental Neurology·Thomas Wichmann
Mar 21, 2007·Journal of the Neurological Sciences·Eduardo López-LasoRafael Artuch
May 4, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Li CaoSheng-Di Chen
Mar 25, 2008·Pediatric Neurology·Benjamin N R CheyetteGregory M Enns
Sep 11, 2013·Parkinsonism & Related Disorders·Jee-Young LeeBeom S Jeon
Apr 28, 2021·Molecular Genetics and Metabolism·Nastassja HimmelreichBeat Thöny

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