ABSTRACT
<p><b>OBJECTIVE</b>To identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation.</p><p><b>METHODS</b>The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>There were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family.</p><p><b>CONCLUSION</b>The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.</p>
Subject(s)
Adult , Child , Female , Humans , Male , Middle Aged , Asian People , Genetics , Base Sequence , Genes, Dominant , Leukoencephalopathies , Genetics , Molecular Sequence Data , Mutation, Missense , Pedigree , Receptor, Macrophage Colony-Stimulating Factor , GeneticsABSTRACT
Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a rare autosomal dominant leukoencephalopathy disease, and colony stimulating factor 1 receptor (CSF1R) is the only gene in which mutations are known to cause HDLS. HDLS should be suspected in individuals with progressive neurological decline, characteristic MR imaging findings, and positive family history. This article reviews recent advance in imaging findings, clinical manifestations, genetic counseling and management in HDLS.
Subject(s)
Humans , Brain , Diagnostic Imaging , Leukoencephalopathies , Diagnosis , Diagnostic Imaging , Genetics , Radiography , Spheroids, Cellular , Cell BiologyABSTRACT
The calcium gate encoded by CCH1 and MID1 genes is the main channel for external calcium absorption. As one of the important secondary messengers, the elevation of calcium concentration could activate some pathways to take part in various cell processes. In this study, we used CCH1 and MID1 mutant strains and also constructed their complementary strains to study the effect of drug tolerance and virulence of Candida albicans after CCH1 or MID1 deletion. By drug plate sensitivity assay and the broth microdilution method, we compared the changes between different strains. Moreover, we added calcium channel blocker and inhibitors to analyze the effect of calcium concentration on drug action. After the deletion of CCH1 or MID1 gene, the strain exhibited an obvious sensitivity to FLUC and ITRA, and the drug action was regulated by the calcium concentration. In a mouse model of intravenous infection, we found that attenuated virulence of cch1delta/delta or mid1delta/delta strain is specifically due to a loss of CCH1 or MID1 gene.
Subject(s)
Animals , Female , Mice , Calcineurin , Genetics , Metabolism , Calcium , Metabolism , Calcium Channels , Metabolism , Candida albicans , Genetics , Virulence , Candidiasis , Microbiology , Drug Resistance, Fungal , Genetics , Fungal Proteins , Genetics , Metabolism , Gene Deletion , Mice, Inbred ICR , VirulenceABSTRACT
Objective To study the effects of eliminating free radical and increasing antioxidative capacity of glutathione peroxidase 1(GPX1) on PC12 cells. MethodsGPX1 recombinant plasmid and Plncxplasmid were transfected into PC12 cells and PC12 cells highly-expressing GPX1 stably were sieved by G418 solution. PC12 ceils were treated with different concentrations of amyloid β-protein (Aβ25-35) for 48 h, to decide the optimal concentration of Aβ25-35 and construct ideal cell model. GPX1/pLNCX/PC12 group, pLNCX/ PC12 group and PC12 group were treated with optimal concentration of Aβ25-35 ,respectively for 48 h, and their absorbance (A) value by MTT conversion was compared among three groups.ResultsCell clone highly expressing GPX1 stably were obtained by G418 selection. The increment of cell inhibition ratio was 24.7 ％ after 20 μmol/L Aβ25-35 treatment for 48 h, compared with control group (P＜0.01). Thus the optimization concentration of Aβ25-35 was 20 μmol/L. After treatment with 20 μmol/L for 48 h, the A value was significantly higher in GPX1/pLNCX/PC12 group than in pLNCX/ PC12 group and in PC12 cells group(0.53±0. 02 vs. 0.44±0.02;0.53±0.02 vs. 0.39±0.07, P＜0.01). Conclusions Transfection of GPX1 recombinant plasmid may protect cell against injury from free radical and reverse the decrease of PC12 cell survival rate impaired by Aβ25-35.