Dopa-responsive infantile hypokinetic rigid syndrome due to dominant guanosine triphosphate cyclohydrolase 1 deficiency

López‐Laso, Eduardo; Camino, Rafael; Mateos, María Elena; Pérez-Navero, Juan Luís; Ochoa, Julio J.; Lao-Villadóniga, José Ignacio; Ormazábal, Aída; Artuch, Rafael

doi:10.1016/j.jns.2007.02.007

Cited by 16 publications

(14 citation statements)

References 13 publications

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“…One patient presented with isolated bilateral resting leg tremor similar to other cases previously reported [17]. We also found a unique case of infantile dopa-responsive hypokinetic rigid syndrome [11].…”

Section: Discussionsupporting

confidence: 82%

“…Subsequently, two apparently unrelated children from the same village (index cases) presented with an infantile hypokinetic rigid syndrome (case VI7) and childhood onset dystonia (case VI10).They responded dramatically to low doses of L-dopa. The clinical features of patient VI7 have been described elsewhere [11]. Family history and clinical examination revealed an inherited disorder.…”

Section: Subjectsmentioning

confidence: 93%

“…Patient IV1 of Family 2 had a beta-CIT SPECT scan compatible with PD. A unique patient with an infantile dopa-responsive hypokinetic rigid syndrome has been described elsewhere (VI7) [11].…”

Section: Molecular Studies and Clinical Correlationsmentioning

confidence: 99%

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Segawa syndrome due to mutation Q89X in the GCH1 gene: a possible founder effect in Córdoba (southern Spain)

et al. 2009

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Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency is an inborn error of neurotransmitter metabolism, with a prevalence of 0.5 per million, caused by mutations/deletions in the GCH1 gene. The finding of the mutation Q89X in the GCH1 gene in 23 patients from two pedigrees in an area inhabited by a population of 800,000 prompted us to consider that our cohort may have descended from a single founder. Twelve Q89X mutation-positive cases belonging to two families and 100 unrelated control subjects from the same geographical region were studied. Six microsatellite markers located near GCH1 were analyzed to validate a possible mutation-related founder haplotype. Haplotype analysis revealed two different haplotypes for six microsatellite markers that segregated with the Q89X mutation. A common haplotype in 10 out of 12 mutation carriers studied was identified. Two subjects carried a second haplotype, most probably because of a recombination event. However, at least 186 different haplotypes were established in the control subjects. In contrast with the frequencies of 83.3% and 16.7%, respectively, found for both mutation-segregating haplotypes, the frequency of none of the control haplotypes exceeded 1.5%. Dystonia was the most frequent symptom in our series, and parkinsonism was present in five patients. The large number of Q89X mutation carriers in our community is because of a founder effect. The same mutation in GCH1 causes a wide phenotypic spectrum of clinical variability occurring in this population of affected patients.

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Section: Discussionsupporting

confidence: 82%

Section: Subjectsmentioning

confidence: 93%

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Segawa syndrome due to mutation Q89X in the GCH1 gene: a possible founder effect in Córdoba (southern Spain)

et al. 2009

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“…The main clinical features of dopa-responsive dystonia are onset of dystonia at 4-8 years of age, usually in the lower limbs, causing an abnormal gait, diurnal fl uctuation of signs and symptoms and other associated features such as hyperrefl exia and extensor plantar refl exes, parkinsonian signs (such as mask faces), or tremor [1][2][3][4][5]15,16 . Although diurnal variation is a typical feature of DRD, characterized by worsening of symptoms from day to day and improving after sleep, as in our patient, such marked fl uctuation is present only in half patients with DRD [1][2][3][4][5]15 .…”

Section: Discussionmentioning

confidence: 99%

“…Although diurnal variation is a typical feature of DRD, characterized by worsening of symptoms from day to day and improving after sleep, as in our patient, such marked fl uctuation is present only in half patients with DRD [1][2][3][4][5]15 . DRD patients can have a marked intrafamilial variability of the clinical manifestations between affected members of the same family 14,16 .…”

Section: Discussionmentioning

confidence: 99%

A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia

Scola

Carducci

Amaral

et al. 2007

Arq. Neuro-Psiquiatr.

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-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.KEY WORDS: dystonia, levodopa, dopa-responsive dystonia, guanosine triphosphate cyclohydrolase 1, GCH1 gene. Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsivaRESUMO -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.

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Human inhibitor of growth 1 inhibits hepatoma cell growth and influences p53 stability in a variant-dependent manner #

Zhu

Luo

et al. 2009

Hepatology

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Dopa-responsive infantile hypokinetic rigid syndrome due to dominant guanosine triphosphate cyclohydrolase 1 deficiency

Cited by 16 publications

References 13 publications

Segawa syndrome due to mutation Q89X in the GCH1 gene: a possible founder effect in Córdoba (southern Spain)

Segawa syndrome due to mutation Q89X in the GCH1 gene: a possible founder effect in Córdoba (southern Spain)

A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia

Human inhibitor of growth 1 inhibits hepatoma cell growth and influences p53 stability in a variant-dependent manner #

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