ABSTRACT
BACKGROUND: Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. CASE PRESENTATION: We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. CONCLUSION: To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.
Subject(s)
Listeria monocytogenes/genetics , Meningitis, Listeria/microbiology , Meningoencephalitis/microbiology , Aged , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Brain Abscess/drug therapy , Diagnostic Errors , Female , High-Throughput Nucleotide Sequencing , Humans , Listeria monocytogenes/isolation & purification , Meningitis, Listeria/diagnosis , Meningitis, Listeria/drug therapy , Meningoencephalitis/diagnosis , Meningoencephalitis/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Tuberculosis, Meningeal/diagnosis , Tuberculosis, Meningeal/microbiologyABSTRACT
OBJECTIVE: To analyze the mutation of CX32 gene and related clinical features in Chinese Han patients with Charcot-Marie-Tooth (CMT) disease. METHODS: Thirty-four CMT families, from 2004 to 2011 at Departments of Neurology, Xiangya Hospital, Third Xiangya Hospital and National Key Laboratory of Medical Genetics, were selected for CX32 mutation screening after the exclusion of the PMP22 duplication and male-to-male transmission. Mutation analysis was carried out by polymerase chain reaction (PCR) plus direct sequencing. Analyses of clinical, electrophysiological and pathological features in 11 patients from 6 CMTX1 families were performed by 2 neurologists. RESULTS: Five CX32 gene mutations were detected in 6 CMT families: c.37G > A, c.65G > A, c.246C > G, c.256A > G and c.533A > G. Among them, c.246C > G and c.533A > G were firstly reported. The clinical manifestations included progressive distal muscle atrophy and weakness, areflexia, sensory abnormalities and pes vacus. Nerve conduction velocity ranged from 21.7 to 49.3 m/s. Both demyelination and axonal degeneration were detected in nerve biopsy. CONCLUSIONS: CMT1X has a frequency of around 9% in our study. The male patients tend to have more serious clinical features and their electrophysiological and pathological changes are intermediate. CX32 mutation analysis helps to confirm the genetic diagnosis of CMT so as to provide genetic counseling and reproductive guidance and elucidate its pathogenesis.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Connexins/genetics , Mutation , Asian People/genetics , Charcot-Marie-Tooth Disease/diagnosis , DNA Mutational Analysis , Female , Humans , Male , Pedigree , Gap Junction beta-1 ProteinABSTRACT
OBJECTIVE: To observe the cellular expression of (R127W) HSPB1 and its influence on neurofilament light chain (NFL) self-assembly and co-localization with NFL. METHODS: Eukaryotic expression vectors pEGFPN1-(wt) HSPB1 and pEGFPN1- (R127W) HSPB1 were constructed. Hela cells were transiently transfected with pEGFPN1-(wt) HSPB1 or pEGFPN1- (R127W) HSPB1 and observed under a confocal microscope. Hela cells were also transiently co-transfected with Pcl-NFL and pEGFPN1-(wt)HSPB1, or pCL-NFL and pEGFPN1-(R127W)HSPB1. The self-assembly of NFL was observed and the co-localization study of HSPB1/ (R127W)HSPB1 with NFL was carried out in these two cell models by immunofluorescence technique. RESULTS: The aggregates formed by EGFP-(R127W)HSPB1 predominantly located around the nucleus, and EGFP-(wt)HSPB1 showed diffusion pattern in Hela cells. When co expressed with EGFP-(wt)HSPB1, NFL formed homogeneous structure in cytosol. When co-expressed with EGFP-(R127W)HSPB1, however, NFL had amorphous staining pattern predominantly consisting of NFL aggregates, and NFL co-localized with (R127W)HSPB1 in these aggregates. CONCLUSION: The R127W mutant of HSPB1 may have reduced capacity to serve as a chaperone to prevent aggregate formation, and fail to correctly organize the neurofilament network. Dysfunction of the axon cytoskeleton and axon transport may be the primary mechanism of R127W mutation of HSPB1 in the pathogenesis of Charcot-Marie-Tooth disease.
