GTP Cyclohydrolase Functions in Fish Color Formation / 中国生物化学与分子生物学报

Guanosine triphosphate cyclohydrolase (GTP cyclohydrolase,Gch) is a protease with a GTP- cyclohydro domain, which is widely found in vertebrates and invertebrates.Mammals and birds only have Gch 1.In teleost and amphibian, other two paralogs (Gch2 and Gch3) also exists besides Gchl, which also displayed functional differences.Gch is a rate-limiting enzyme that ultimately synthesized the tetrahydrobiopterin (BH4) using guanosine triphosphate as a substrate.BH4 is an essential coenzyme of aromatic amino acid hydroxylase and contributes to the synthesis of various hormones and neurotransmitters.The Gch is an initial step in the catalysis of various pterin biosynthesis and plays important roles in a series of physiological and pathological processes, such as skin pigmentation, ocular pigmentation, methotrexate, folic acid, and tetrahydrobiopterin.The physiological function of Gch is inextricably linked to the biosynthesis of BH4.As the only rate-limiting enzyme in BH4 biosynthesis, the activity of Gch is a useful indicator for the development of neurons and pigment cells.Besides, it is also an important marker of pigment synthesis and neurotransmitter biosynthesis.Nowadays, the functions of Geh in pathogenesis of tumor and cardiovascular diseases have been widely concerned, while the researches on the pigmentation and color formation are mainly concentrated in insects, and rarely in teleost.Therefore, this article summarized the characteristics of Gch genes, protein and the functions of Gch in fish coloration, which has important guiding significance for further illustration the mechanism of Gch in teleost pigmentation and fish color genetic improvements.

Ensayo de reproducción inducida en Ariopsis seemanni / Induced spawning trial with Ariopsis seemanni / Ensajo de reprodução induzida em Ariopsis seemanni

Resumen El bagre marino Ariopsis seemanni es aprovechado como pez de consumo en la alimentación de pescadores y pobladores de la región pacifica colombiana y como pez ornamental (5 a 10 cm -longitud total), a nivel comercial nacional e internacional. En Colombia esta especie ha sido priorizada en la agenda nacional de investigación en acuicultura de 2011-2012, como una de las especies marinas potenciales en actividades acuícolas. El objetivo de esta investigación fue evaluar el efecto de la gonadotropina coriónica humana (HGC) y el extracto pituitario de carpa (EPC) sobre la maduración final y el desove en hembras adultas de la especie. Se utilizaron 24 parejas de peces silvestres capturadas del medio, con un peso promedio de 263.6±42.2 g y 174.4±30.4 g para hembras y machos, respectivamente. Se utilizaron cuatro tratamientos hormonales: T1: 5 mg EPC/kg; T2: 7 mg EPC/kg; T3: 2000 UI HGC/kg y T4: 1000 UI HGC/kg. Se identificaron tres tipos de oocitos en maduración, no se presentaron diferencias estadísticamente significativas (p>0,05) entre los tratamientos utilizados y la cantidad de oocitos en maduración; no se obtuvo desove espontaneo en ninguna de las hembras inducidas con las dosis hormonales empleadas.

Abstract The tete sea catfish Ariopsis seemanni is a fish used for human consumption by fishermen and residents along the coast of Colombia and as ornamental fish (5 to 10 cm -total longitude), at national and international comercial level. In Colombia, this species has been prioritized in the national aquaculture research agenda 2011-2012, as one of the potential marine species for aquaculture activities. This research was aimed at evaluating the effect of human chorionic gonadotropin (HGC) and carp pituitary extract (EPC) on final maturation and spawning adult females of the species. 24 pairs of wild fish were used, with an average weight of 263.6±42.2 g and 174.4±30.4 g for females and males, respectively. Four hormonal treatments was be used: T1: EPC 5 mg/kg; T2: EPC 7 mg/kg; T3: HGC 2000 IU/kg and T4: HGC 1000 IU/kg. Identify three types of maturation oocytes was. There were no statistically significant differences (p>0,05) between treatments used and the number of oocytes achieving maturation. No spontaneous spawning was obtained in any of the females induced with the hormonal doses used.

Resumo O bagre marino Ariopsis seemanni é aproveitado como peixe de consumo na alimentação de pescadores e moradores da região pacifica colombiana e como peixe ornamental (5 a 10 cm de comprimento), a nível comercial nacional e internacional. Na Colômbia A. seemanni tem sido priorizado na agenda nacional de pesquisa na aquicultura de 2011-2012, como uma das espécies marinhas potenciais em atividades aquícolas. Esta pesquisa teve como objetivo avaliar o efeito da gonadotrofina coriónica humana (GCH) e o extrato pituitário de carpa (EPC) sobre a maduração final e o desove em fêmeas adultas desta espécie. Utilizaram-se 24 casais de peixes retirados do meio natural, com um peso médio de 263,6 ± 42,2 g e 174,4 ± 30,4 g para fêmeas e machos, respectivamente. Empregaram-se quatro tratamentos hormonais: T1: 5 mg EPC/kg; T2: 7 mg EPC/kg; T3: 2000 UI HGC/kg e T4: 1000 UI HGC/kg. Identificaram-se três tipos de oócitos em maduração, não houve diferencias estatisticamente significativas (p>0,05) entre os tratamentos utilizados e a quantidade de oócitos em maturação; não foi possível obter desove espontâneo em nenhuma das fêmeas induzidas com as doses hormonais empregadas.

Changes in methylation status of the whole genome and GCH1 gene in patients with herpes zoster neuralgia / 中华皮肤科杂志

Objective To analyze the correlation between herpes zoster neuralgia and the methylation status of the whole genome and GCH1 gene.Methods From June to October in 2017,patients with confirmed herpes zoster and obvious neuralgia were selected in Department of Dermatology,The Affiliated Hospital of Xuzhou Medical University,who achieved complete remission (no effect was observed on normal sleep) of neuralgia after antiviral and neurotrophic treatment.Finally,36 patients and 36 healthy controls were enrolled into this study.Peripheral blood samples were obtained from the healthy controls and patients before and after the treatment.Dot-blot hybridization assay was performed to determine the methylation status of the whole genome,methylated-DNA IP kit was used to enrich the methylation sites of the GCH1 gene,and real-time quantitative PCR was conducted to detect changes in methylation status of the GCH1 gene.Statistical analysis was carried out with GraphPad Prism v7.00 software by using paired t test for the comparison of methylation status before and after the treatment,and two-sample t test for the comparison between the patient group and control group.Results The relative methylation level of the whole genome was 135.94 ± 2.52 in the patients before treatment,significantly lower than that in the patients after treatment (144.76 ± 3.48,t =2.056,P ＜ 0.05) and healthy control group (146.84 ± 3.39,t =2.580,P ＜ 0.05).However,there was no significant difference in the methylation status of the whole genome between the patients after treatment and healthy controls (t =0.429,P ＞ 0.05).Compared with the patients after treatment (0.89 ± 0.13) and healthy control group (0.97 ± 0.07),the methylation status of the GCH1 gene significantly decreased in the patients before treatment (0.65 ± 0.17;t =3.977,4.648 respectively,P ＜ 0.05,＜ 0.01 respectively),while no significant difference between the patients after treatment and the healthy controls (t =0.506,P ＞ 0.05).Conclusion The methylation status of the whole genome and GCH 1 gene markedly decreased in the patients with herpes zoster neuralgia.

Analysis of GCH1 gene mutation of close relatives marriage caused dopa reactive dystonia ( report of one family) / 临床神经病学杂志

Objective To analyze the characteristics of GCH1 gene mutation of close relatives marriage caused dopa reactive dystonia (DRD).Methods The data of 3 patients with DRD from the same family in our hospital and their families were analyzed.Genes related to hereditary dyskinesia in their families were detected and validated. Results In this family, the proband’s parents (Ⅲ3 and Ⅲ4) were close relatives.The proband (Ⅳ2) and her eldest daughter (Ⅴ2) and niece (Ⅴ7) were all DRD patients.All of them were young onset , mainly manifested as Parkinsonina-like symptoms and dystonia , and all responded well to dopamine therapy.Gene detection showed that the GCH1 gene had c.245T＞C (p.Leu82Pro) mutation.The second daughter (Ⅴ3), son (Ⅴ5), granddaughter (Ⅵ3) and brother (Ⅳ3) of the proband were carriers of abnormal genes.Conclusions Close relatives marriage increases the incidence of DRD.DRD may be considered in patients with a positive family history of dystonia.Gene detection is an effective diagnosis method.

A Case of Dopa-responsive Dystonia with a Mutation in the GCH1 Gene Misdiagnosed as Cerebral Palsy for 2 Years / 대한소아신경학회지

Dopa-responsive dystonia (DRD) is characterized by lower limb-onset, diurnally fluctuating dystonia and dramatic and sustained response to levodopa treatment. Segawa disease, an autosomal dominant deficiency of guanosine triphosphate cyclohydrolase 1 (encoded by GCH1) is the most common and well-known condition manifesting as DRD. However, similar clinical manifestations can be seen in individuals with deficiencies of other enzymes that are involved in the biosynthesis of dopamine. We describe the case of an 11-year-old girl who presented with abnormal gait, which had initially begun 2 years back. The patient showed diurnally fluctuating dystonia in both legs. She was able to walk without support in the morning, but was unable to stand without support in the evening. She had been diagnosed as having spastic cerebral palsy and had been managed with physical therapy at a local rehabilitation clinic. The patient had been healthy until the development of dystonia, and did not have a history of perinatal problems or developmental delay. Routine hematologic and biochemical test results were normal. Brain magnetic resonance imaging and electroencephalography showed no abnormalities. When levodopa was administered, the patient's abnormal gait dramatically improved 1 hour after receiving the medication. Genetic testing for the GCH1 gene revealed a missense mutation (c.293C>T [p.A98V]) that has previously been reported in patients with DRD. This case demonstrated that a levodopa trial is vital for accurate and early diagnosis of DRD in patients with dystonia resulting from an unknown cause.

Dopa-responsive Dystonia with a Novel Initiation Codon Mutation in the GCH1 Gene Misdiagnosed as Cerebral Palsy

Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by childhood-onset dystonia and a dramatic response to relatively low doses of levodopa. However, patients with DRD can be misdiagnosed as cerebral palsy or spastic diplegia due to phenotypic variation. Here we report a young woman with DRD who were severely disabled and misdiagnosed as cerebral palsy for over 10 yr. A small dose of levodopa restored wheelchair-bound state to normality. However, thoracolumbar scoliosis has remained as a sequel due to late detection of DRD. Genetic analysis by using PCR-direct sequencing revealed a novel initiation codon mutation (c.1A>T; p.Met1Leu) in GTP cyclohydrolase 1 (GCH1) gene. Although it is known that DRD can be misdiagnosed as cerebral palsy, this case reinforces the importance of differential diagnosis of DRD from cerebral palsy.

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

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.

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.