RESUMEN
Objective To explore the clinical and genetic characteristics, treatment. and prognosis of dopamine responsive dystonia (DRD) in children. Method The clinical data of DRD in 3 children admitted to neurology clinic from January 2014 to August 2017 were retrospectively analyzed. Results Two male children, 20-month-old and 2-year-old respectively, and one 4-year-old female child suffered from hypotonia after birth or one year after birth. Genetic testing found that case 1 had heterozygous mutations in tyrosine hydroxylase (TH) gene, C. G943A (p. G315S) from his mother (PMID 20056467) and C. G739A (p. G247S) from his father (PMID 18554280, 24753243) . Case 2 had a heterozygous mutation, c.454-2A＞G, in GCH-1 gene, which was identified to be from his father (PMID 10732814) . Case 3 had two mutations in TH1 gene, c.580+2T>C from her mother (novel mutation) and c.698G>A (p.R233H) from her father (PMID 9703425) . The mother of case 1 was pregnant again. Prenatal examination revealed that the fetus only carried c.G943A (p.G315S) from the mother. Three patients were treated with a small dose of madopar after diagnosis, and gradually increased to obtain the best effect. After 6-month follow-up, cases 1 and 2 recovered to normal, and case 3 showed significant improvement in dystonia, but left foot deformity. Conclusion DRD can start in infants and young children with atypical early symptoms. Genetic testing can make a definite diagnosis. The family that has proband should undergo prenatal examination.
RESUMEN
Aim To investigate TH and GDNF genes expression and regulation of lentivirus ( Lv-TH-GDNF ) based on improved Tet-On system and the effect of the Lv-TH-GDNF intrastriatal transfer on a rat Parkinson’ s disease( PD) model. Methods 1. HeLa cells were infected by obtained Lv-TH-GDNF and rtTA2 s-M2 vi-rus. The expression of tyrosine hydroxylase ( TH ) and glial cell line-derived neurotrophic factor( GDNF) genes was induced by doxycycline( Dox) which was examined by Western blot. 2. The Lv-TH-GDNF together with rtTA2 s-M2 viruses were injected into lesion-side stria-tum of a rat PD model, and the expression of GDNF and TH genes was induced by Dox. Then, the effects of Lv-TH-GDNF were evaluated by the apomorphine-induced rotational behavior, the number of dopaminer-gic neurons in substantia nigra,DA and DOPAC levels in the lesion-side striatum. In addition, Western blot was performed to check the expression of TH and GD-NF genes in the transplanted striatum. Results 1. In vitro studies on HeLa cells, Western blot showed clear protein bands of TH and GDNF in the Dox-positive group, but not in the Dox-negative group. 2. In vivo experiments in animals, the results showed that, 4 weeks after transplantation, the apomorphine-induced turning effect was significantly improved ( P<0 . 01 ) , the number of TH-positive cells in the lesion-side sub-stantia nigra pars compacta as well as the content of DA and DOPAC, the protein level of GDNF and TH genes in the lesion-side striatum was significantly in-creased ( P<0 . 01 ) , each of which was only in Lv-TH-GDNF+rtTA2 s-M2+Dox-treated rats as compared with PBS-treated rats. Conclusion The expression of TH and GDNF genes in Lv-TH-GDNF based on im-proved Tet-On system is effectively regulated by tetra-cycline antibiotics without basal activity in vitro, and the intrastriatal transfer of which has certain therapeutic effect on PD rats.