A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva
Dopa-responsive dystonia (DRD) is an inherited metabolic disorder now classified as DYT5 with two different biochemical defects: autosomal dominant GTP cyclohydrolase 1 (GCH1) deficiency or autosomal recessive tyrosine hydroxylase deficiency. We report the case of a 10-years-old girl with progressiv...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Academia Brasileira de Neurologia (ABNEURO)
2007-12-01
|
| Series: | Arquivos de Neuro-Psiquiatria |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2007000700026 |
| _version_ | 1818322158204485632 |
|---|---|
| author | Rosana H. Scola Carla Carducci Vanise G. Amaral Paulo J. Lorenzoni Helio A.G. Teive Teresa Giovanniello Lineu C. Werneck |
| author_facet | Rosana H. Scola Carla Carducci Vanise G. Amaral Paulo J. Lorenzoni Helio A.G. Teive Teresa Giovanniello Lineu C. Werneck |
| author_sort | Rosana H. Scola |
| collection | DOAJ |
| description | Dopa-responsive dystonia (DRD) is an inherited metabolic disorder now classified as DYT5 with two different biochemical defects: autosomal dominant GTP cyclohydrolase 1 (GCH1) deficiency or autosomal recessive tyrosine hydroxylase deficiency. We report the case of a 10-years-old girl with progressive generalized dystonia and gait disorder who presented dramatic response to levodopa. The phenylalanine to tyrosine ratio was significantly higher after phenylalanine loading test. This condition had two different heterozygous mutations in the GCH1 gene: the previously reported P23L mutation and a new Q182E mutation. The characteristics of the DRD and the molecular genetic findings are discussed.<br>Distonia dopa-responsiva (DRD), classificada como DYT5, é um erro inato do metabolismo que pode ser causado por dois diferentes tipos de defeito bioquímico: deficiência de GTP ciclo-hidrolase 1 (GCH1) (autossômica dominante) ou de tirosina hidroxilase (autossômica recessiva). Descrevemos o caso de menina de 10 anos com distonia generalizada progressiva e alteração da marcha com importante melhora após uso de levodopa. A relação fenilalanina/tirosina estava aumentada após teste de sobrecarga com fenilalanina. O estudo molecular mostrou que o paciente apresenta uma combinação hererozigótica de mutação no gene GCH1: a já conhecida mutação P23L e uma nova mutação Q182E. Discutem-se as características da DRD e as alterações genéticas possíveis. |
| first_indexed | 2024-12-13T10:52:21Z |
| format | Article |
| id | doaj.art-01dcbe5625bd4222bca5f5a0d91c04f5 |
| institution | Directory Open Access Journal |
| issn | 0004-282X 1678-4227 |
| language | English |
| last_indexed | 2024-12-13T10:52:21Z |
| publishDate | 2007-12-01 |
| publisher | Academia Brasileira de Neurologia (ABNEURO) |
| record_format | Article |
| series | Arquivos de Neuro-Psiquiatria |
| spelling | doaj.art-01dcbe5625bd4222bca5f5a0d91c04f52022-12-21T23:49:45ZengAcademia Brasileira de Neurologia (ABNEURO)Arquivos de Neuro-Psiquiatria0004-282X1678-42272007-12-01654b1224122710.1590/S0004-282X2007000700026A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsivaRosana H. ScolaCarla CarducciVanise G. AmaralPaulo J. LorenzoniHelio A.G. TeiveTeresa GiovannielloLineu C. WerneckDopa-responsive dystonia (DRD) is an inherited metabolic disorder now classified as DYT5 with two different biochemical defects: autosomal dominant GTP cyclohydrolase 1 (GCH1) deficiency or autosomal recessive tyrosine hydroxylase deficiency. We report the case of a 10-years-old girl with progressive generalized dystonia and gait disorder who presented dramatic response to levodopa. The phenylalanine to tyrosine ratio was significantly higher after phenylalanine loading test. This condition had two different heterozygous mutations in the GCH1 gene: the previously reported P23L mutation and a new Q182E mutation. The characteristics of the DRD and the molecular genetic findings are discussed.<br>Distonia dopa-responsiva (DRD), classificada como DYT5, é um erro inato do metabolismo que pode ser causado por dois diferentes tipos de defeito bioquímico: deficiência de GTP ciclo-hidrolase 1 (GCH1) (autossômica dominante) ou de tirosina hidroxilase (autossômica recessiva). Descrevemos o caso de menina de 10 anos com distonia generalizada progressiva e alteração da marcha com importante melhora após uso de levodopa. A relação fenilalanina/tirosina estava aumentada após teste de sobrecarga com fenilalanina. O estudo molecular mostrou que o paciente apresenta uma combinação hererozigótica de mutação no gene GCH1: a já conhecida mutação P23L e uma nova mutação Q182E. Discutem-se as características da DRD e as alterações genéticas possíveis.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2007000700026distonialevodopadistonia dopa-responsivaguanosina trifosfato ciclo-hidrolase 1gene GCH1dystonialevodopadopa-responsive dystoniaguanosine triphosphate cyclohydrolase 1GCH1 gene |
| spellingShingle | Rosana H. Scola Carla Carducci Vanise G. Amaral Paulo J. Lorenzoni Helio A.G. Teive Teresa Giovanniello Lineu C. Werneck A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva Arquivos de Neuro-Psiquiatria distonia levodopa distonia dopa-responsiva guanosina trifosfato ciclo-hidrolase 1 gene GCH1 dystonia levodopa dopa-responsive dystonia guanosine triphosphate cyclohydrolase 1 GCH1 gene |
| title | A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva |
| title_full | A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva |
| title_fullStr | A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva |
| title_full_unstemmed | A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva |
| title_short | A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsiva |
| title_sort | novel missense mutation pattern of the gch1 gene in dopa responsive dystonia novo padrao de mutacao missense no gene gch1 na distonia dopa responsiva |
| topic | distonia levodopa distonia dopa-responsiva guanosina trifosfato ciclo-hidrolase 1 gene GCH1 dystonia levodopa dopa-responsive dystonia guanosine triphosphate cyclohydrolase 1 GCH1 gene |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2007000700026 |
| work_keys_str_mv | AT rosanahscola anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT carlacarducci anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT vanisegamaral anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT paulojlorenzoni anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT helioagteive anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT teresagiovanniello anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT lineucwerneck anovelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT rosanahscola novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT carlacarducci novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT vanisegamaral novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT paulojlorenzoni novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT helioagteive novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT teresagiovanniello novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva AT lineucwerneck novelmissensemutationpatternofthegch1geneindoparesponsivedystonianovopadraodemutacaomissensenogenegch1nadistoniadoparesponsiva |