ABSTRACT
OBJECTIVE@#To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis.@*METHODS@#Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic.@*CONCLUSION@#The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
Subject(s)
Humans , China , Mutation , Pedigree , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 2 Protein/geneticsABSTRACT
Objective To explore the effect of hydrogen sulfide (H2S) on corticosterone (CORT) -induced neuronal and synaptic damages in the hippocampus of depression rat models.Methods Adult male SD rats were randomly divided into 4 groups:control group,CORT group,low-concentration NaHS (30 μmol/kg) treatment group and high-concentration NaHS (100 μmol/kg) treatment group (n=10).CORT (40 mg/kg) was subcutaneously injected into the rats from the later three groups for 28 d to establish depression models.After administration of CORT for 14 d,the control rats and CORT rats were treated with normal saline (5 mL/kg,ip) for 14 d,rats in the later two groups were treated with NaHS (30 and 100 μmol/kg/d,ip) for 14 d.The depressive-like behaviors were evaluated by sucrose preference test,the neuronal pathological changes in the hippocampus CA3 area were observed by HE staining,the neuronal apoptosis in the hippocampus was observed under microscope using Tunel staining,the protein expressions of Bcl-2,Bax and synaptophysin in the hippocampus were quantified by Western blotting,and the content of Caspase-3 was analyzed by ELISA.Results After administration of CORT for 28 d,rats from the CORT group exhibited decreased sucrose preference,disordered arrangement and sparse morphology as well as increased amount of apoptotic neuron in hippocampal CA3 area as compared with those in the control group with significant differences (P＜0.05);in addition,as compared with those in the control group,the expressions of Bcl-2 and SYN in the hippocampus were significantly suppressed,while the activity of Caspase-3 and the expression of Bax in hippocampus were significantly up-regulated in the rats firom the CORT group (P＜0.05).As compared with CORT group,low-concentration NaHS treatment group and high-concentration NaHS treatment group had significantly increased sucrose preference,improved arrangement of neurons,decreased amount of apoptotic neurons in CA3 areas of CORT rats,up-regulated Bcl-2 and Syn expressions,down-regulated Bax expression as well as reduced activity of Caspase-3 in the hippocampus,with statistically significant differences (P＜0.05);but there was no significant difference between low and high concentration NaHS treatment groups (P＞0.05).Conclusion H2S can effectively improve the damage of hippocampal neurons and synapses in CORT rats.