Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

The association of tyrosine hydroxylase gene polymorphism with mental disorder / 法医学杂志

OBJECTIVE@#To evaluate the relationship between the tyrosine hydroxylase (TH) gene and mental disorder by comparing the two TH gene SNP points (extron 3 and intron 9) of patients with mental disorders and normal human.@*METHODS@#DNA extracted from specimens of patients and normal subjects were quantified by using Real-time PCR.@*RESULTS@#(1) G334A distribution was: G=0.133, A=0.867 in patients with schizophrenia, G=0.116, A=0.884 in patients with depression, and G=0.214, A=0.786 in normal group. (2) C5162G distribution was: C=0.962, G=0.038 in patients with schizophrenia, C=0.959, G=0.041 in patients with depression, and C=0.961, G=0.039 in normal group.@*CONCLUSION@#There are statistically significant differences in G334A locus between normal people and patients with mental disorders, but no statistically significant differences in C5162G locus.

Molecular genetics of schizophrenia: past, present and future.

Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance which is also governed by non-genetic factors. Candidate genes identified on the basis of biochemical and pharmacological evidence are being tested for linkage and association studies. Neurotransmitters, especially dopamine and serotonin have been widely implicated in its etiology. Genome scan of all human chromosomes with closely spaced polymorphic markers is being used for linkage studies. The completion and availability of the first draft of Human Genome Sequence has provided a treasure-trove that can be utilized to gain insight into the so far inaccessible regions of the human genome. Significant technological advances for identification of single nucleo-tide polymorphisms (SNPs) and use of microarrays have further strengthened research methodologies for genetic analysis of complex traits. In this review, we summarize the evolution of schizophrenia genetics from the past to the present, current trends and future direction of research.

Perspectivas de la terapia génica en la enfermedad de Parkinson / Perspectives of the genic therapy in the Parkinson's disease

En la enfermedad de Parkinson idiopática, así como en algunos otros parkinsonismos, la actual estrategia terapéutica sigue basándose en el uso de fármacos y otros procedimientos destinados a "normalizar" la neurotransmisión dopaminérgica central. Cuando un enfermo parkinsoniano debuta con su sintomatología clínica, ya ha perdido aproximadamente un 80 por ciento de las neuronas dopaminérgicas nigrales, lo cual se manifiesta en una reducción de aproximadamente dos órdenes de magnitud de las concentraciones estriatales de dopamina