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BACKGROUND: Brain microvascular endothelial cell (BMEC) is an important therapeutic target for the inhibition of brain vascular dysfunction in ischemic stroke. Expression of long non-coding RNA SNHG1 is reportedly upregulated in BMEC after OGD. The present study aims to investigate the potential roles of SNHG1 in OGD-induced injury in BMEC. METHODS: Mice primary brain microvascular endothelial cells (BMEC) were cultured under "normal" or "oxygen/glucose-deprived" (OGD) conditions. The expression of SNHG1 and miR-338 after OGD were examined by qPCR. shRNA against SNHG1 was used to knockdown SNHG1 in BMEC. MiR-338-3p mimic and inhibitor were used to change the expression of miR-338 in BMEC. The relationship between SNHG1 and miR-338, and the relationship between miR-338 and HIF-1α were clarified using RNA pull-down and luciferase reporter gene assays, respectively. RESULTS: SNHG1 and miR-338 were upregulated in OGD induced BMEC. SNHG1 silence aggravated OGD-induced cell apoptosis by down-regulating Bcl-2, HIF-1α and VEGF-A, and upregulating caspase 3 activity and Bax. MiR-338 was upregulated in SNHG1-silenced BMEC. RNA pull-down assays showed that SNHG1 could be directly bound by miR-338. In addition, miR-338 overexpression reduced cell viability in OGD while miR-338 inhibition protected BMEC against OGD-induced injury. Furthermore, luciferase reporter assay showed that HIF-1α was a direct target of miR-338. CONCLUSIONS: SNHG1 exerted protective effects against OGD induced injury via sponging miR-338, thus upregulating HIF-1α/VEGF-A in BMEC.
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Células Endoteliales/metabolismo , Glucosa/deficiencia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Apoptosis/genética , Encéfalo/metabolismo , Supervivencia Celular/genética , Células Endoteliales/patología , Endotelio/metabolismo , Glucosa/metabolismo , Hipoxia/genética , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Oxígeno/metabolismo , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR) Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1 probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL, and RAB7. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics (ACMG). Clinical features were reevaluated. RESULTS: We identified three novel heterozygous variants such as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of uncertain significance. CONCLUSIONS: SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.
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Enfermedad de Charcot-Marie-Tooth/genética , Subunidades gamma de la Proteína de Unión al GTP/genética , Mutación , Proteína P2 de Mielina/genética , Proteínas/genética , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , MasculinoRESUMEN
Neurodegenerative disorders have attracted attention in last decades due to their high incidence in the world. The p53/miR-34a axis triggers apoptosis and suppresses viability in multiple types of cells, but little is known about its role in neurodegenerative diseases. In this study, we showed that presenilin (PS)-2, a major gene associated with familial Alzheimer's disease (AD) could trigger the apoptosis through the p53/miR-34a axis in PC12 cells. First we found that PC12 cell viability was downregulated by PS-2 and mutant PS-2 overexpression, especially by mutant PS-2 overexpression. Then, we established a mutant PS-2-overexpressing PC12 cell line and confirmed that mutant PS-2 induced not only p53 but also miR-34a expression. The transfection of miR-34a inhibitor reversed PS-2-induced effects on cellular viability and apoptosis. Mutant PS-2 overexpression promoted caspase-3 expression, reduced Sirt1 and Bcl-2 expression, all of which were miR-34a downstream genes related with cell apoptosis. Moreover, mutant PS-2 also activated the p53/miR-34a axis and induced apoptosis in AD transgenic mice brain. These results implied that mutant PS-2 might promote the apoptosis of neuronal cells through triggering the p53/miR-34a axis. Altogether our results provide a novel insight into neurodegenerative disease and deepen our understandings of AD pathogenic processes.
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MicroARNs/metabolismo , Presenilina-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/genética , Animales , Apoptosis/genética , Caspasa 3/metabolismo , Genes p53 , Ratones , Ratones Transgénicos , MicroARNs/genética , Enfermedades Neurodegenerativas/genética , Células PC12 , Presenilina-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismoRESUMEN
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.
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Enfermedad de Charcot-Marie-Tooth/genética , Conexinas/genética , Mutación , Pueblo Asiatico/genética , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Linaje , Proteína beta1 de Unión ComunicanteRESUMEN
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.
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Regulación de la Expresión Génica , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas de Neurofilamentos/metabolismo , Secuencia de Bases , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Vectores Genéticos/genética , Células HeLa , Proteínas de Choque Térmico , Humanos , Espacio Intracelular/metabolismo , Chaperonas Moleculares , Unión Proteica/genética , Transporte de Proteínas , TransfecciónRESUMEN
The purpose of this study was to understand the mutation features of lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), ras-associated protein RAB7 (RAB7), lamin A/C (LMNA) and myotubularin-related protein 2 (MTMR2) genes in Chinese Charcot-Marie-Tooth disease (CMT) patients. Mutation analysis of LITAF gene was carried out using PCR combined with DNA sequencing, and mutation analysis of RAB7 gene by PCR-single strand conformation polymorphism (PCR-SSCP) combined with DNA sequencing in 33 CMT patients including 6 probands of autosomal domi-nated CMT families and 27 sporadic patients; mutation analysis of LMNA and MTMR2 genes was observed using PCR-SSCP combined with DNA sequencing in 41 CMT patients, including 14 probands of autosomal recessive CMT fami-lies and 27 sporadic patients. Two sequence variations c.269G-->A and c.274A-->G were detected in LITAF gene and two sequence variations c.1243G-->A and c.1910C-->T were detected in LMNA gene. No sequence variation was found in RAB7 and MTMR2 gene. Variations of c.269G-->A in LITAF gene and c.1243G-->A, c.1910C-->T in LMNA gene are newly found SNPs in this study. Variation of c.274A-->G in LITAF gene is known SNP reported in SNP database. Mutations in LITAF, RAB7, LMNA, and MTMR2 genes are rare in Chinese CMT patients.
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Enfermedad de Charcot-Marie-Tooth/genética , Lamina Tipo A/genética , Mutación , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatasas no Receptoras/genética , Factores de Transcripción/genética , Proteínas de Unión al GTP rab/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteínas de Unión a GTP rab7RESUMEN
OBJECTIVE: To analyze MFN2 gene mutation in Chinese patients Charcot-Marie-Tooth disease (CMT) and to establish a quick and effective diagnostic method. METHODS: Through denaturing high-performance liquid chromatography (DHPLC) combined with DNA sequencing, MFN2 gene mutation analysis was carried out in 35 Chinese CMT2 patients including 9 probands of CMT2 pedigree and 26 sporadic CMT2 patients. RESULTS: The investigators found three abnormal sequence variations in MFN2 gene: c.281G-->A, c.395G-->A and c.408A-->T. c.395G-->A (C132T) was a novel causative missense mutation firstly reported while c.281G-->A (R94Q) a hotspot mutation and c.408A-->T (V136V) a single nucleotide polymorphism (SNP). The accuracy and specificity of DHPLC detection reached up to 100%. CONCLUSION: Through DHPLC combined with DNA sequencing, MFN2 mutations are detected in Chinese CMT2 patients. There are two causative missense mutations: c.395G-->A (C132T) and c.281G-->A (R94Q) and one SNP c.408A-->T (V136V). Such a method is an effective and economic diagnostic screening tool of MFN2 gene in CMT patients on a large scale.
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Enfermedad de Charcot-Marie-Tooth/genética , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Adolescente , Adulto , Pueblo Asiatico/genética , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Niño , Preescolar , Análisis Mutacional de ADN , Cartilla de ADN , Femenino , GTP Fosfohidrolasas , Humanos , Masculino , Mutación , Linaje , Adulto JovenRESUMEN
OBJECTIVE: To study the possible mechanism of the intracellular aggregate formation of small heat shock protein HSPB8 (HSPB8)(K141N) mutation resulting in axonal Charcot-Marie-Tooth disease type 2L(CMT2L). METHODS: The cell models which transiently expressed pEGFPN1-HSPB8 and pEGFPN1-(K141N)HSPB8 were established. The immunofluorescent co-location study of EGFP-(K141N)HSPB8 and HSPB1, EGFP-(K141N)HSPB8 and neurofilament light chain (NEFL) was carried out in the SHSY5Y cell models. The aggregate formation of EGFP-(K141N)HSPB8 in cell models was investigated and the possible mechanism of cellular aggregate formation was analyzed by t test and analysis of variance between group(ANOVA). RESULTS: EGFP-(K141N)HSPB8 formed large aggregate which predominantly located around the nucleus in cell models. EGFP-(K141N)HSPB8 co-localized perfectly with HSPB1 and NEFL in the SHSY5Y cell models. The aggregate formation was different in different cell types, there were fewer aggregates formed in an sHSPs deficient milieu than in HEK293T cells. CONCLUSION: (K141N)HSPB8 formed aggregates predominantly locate around the nucleus in cells. (K141N)HSPB8 co-localizes perfectly with HSPB1 and NEFL. The aggregate formation may be due to (K141N)HSPB8 conformational change leading to self aggregation and its abnormal interaction with other sHSPs such as HSPB1.
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Enfermedad de Charcot-Marie-Tooth/genética , Proteínas de Choque Térmico/genética , Mutación Puntual , Proteínas Serina-Treonina Quinasas/genética , Línea Celular , Línea Celular Tumoral , Núcleo Celular/metabolismo , Enfermedad de Charcot-Marie-Tooth/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de Choque Térmico HSP27 , Células HeLa , Proteínas de Choque Térmico/metabolismo , Humanos , Riñón/citología , Riñón/metabolismo , Microscopía Confocal , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patología , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , TransfecciónRESUMEN
OBJECTIVE: To clone the disease-causing genes possibly existing in 6.8 cM distance between microsatellite markers D12S1720 and D12S1611 in chromosome 12q24 for Charcot-Marie-Tooth disease type 2L (CMT2L). METHODS: Ten positional and functional candidate genes were chosen among all known genes in this locus region by bioinformatics inqury. Mutation detection was performed by sequencing the exons and intron-exon junctions of the candidate genes. RESULTS: Eleven sequence variations, that included 5 heterozygous and 6 homozygous variations, were detected in the exons and flanking areas of the 10 candidate genes. All the variations showed no co-segregation with disease phenotype. CONCLUSION: Ten candidate genes(TAOK3, RAB35, RPLP0, PXN, RNF10, RHOF, VPS33A, RSN, DENR, RNP24) were ruled out as the disease-causing gene for CMT2L. Ten single nucleotide polymorphisms (SNP) were reported for the first time.
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Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos Par 12/genética , Secuencia de Bases , Clonación de Organismos , ADN/análisis , Análisis Mutacional de ADN , Humanos , Datos de Secuencia Molecular , Técnicas de Amplificación de Ácido NucleicoRESUMEN
OBJECTIVE: To determine the effects of sodiun aescinate on Bcl-2 and Caspase-3 protein expression and neuronal apoptosis after focal cerebral ischemia reperfusion injury in rats. METHODS: One hundred male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) and reperfusion. The rats were divided randomly into 4 groups: sham-operated group and MCAO and reperfusion model groups which were randomly divided into control group, saline group, and sodium aescinate group. The immunohistochemistry staining and microscope image were used to observe the dynamic Bcl-2 and Caspase-3 protein expression in the ischemic penumbra after the reperfusion. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining was performed for the detection of apoptosis. RESULTS: Bcl-2 protein expression in the sodium aescinate group was significantly higher than that of the saline group and control group (P < 0.05). While Caspase-3 protein expression in the sodium aescinate group was then compared with those of the saline group and control group, and showed the difference was significant (P < 0.05). Compared with the saline group and control group, the number of apoptotic cells in the sodium aescinate group was significantly reduced (P < 0.01). CONCLUSION: Sodium aescinate increases Bcl-2 protein expression and decreases Caspase-3 protein expression,through which it can protect the ischemia brain on reperfusion injury.
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Alginatos/farmacología , Apoptosis , Isquemia Encefálica/metabolismo , Caspasas/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Daño por Reperfusión/metabolismo , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/patología , Caspasa 3 , Caspasas/genética , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/farmacología , Masculino , Plantas Medicinales/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Distribución Aleatoria , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Saponinas/farmacologíaRESUMEN
OBJECTIVE: To explore the curative effect of combining exchange of cerebrospinal fluid with small dose of urokinase injection for the treatment of subarachnoid hemorrhage (SAH). METHODS: One hundred thirty-four SAH patients diagnosed by CT or MRI and lumbar puncture were randomly divided into two groups: 68 patients in the treatment group were given exchange of cerebrospinal fluid and small dose of urokinase injection; 66 patients in the control group were treated with exchange of cerebrospinal fluid. The main complications, the neurological deficit scale and curative effect of the two groups were compared. RESULTS: Complications about cerebral vasospasm and hydrocephalus were fewer than those in the conventional therapeutic group (P < 0.05), and there was no significant difference in the incidence of rebleeding between the two groups (P > 0.05). The neurological deficit scale in the treatment-group was significantly lower than that in conventional therapeutic group (P < 0.01). There was obvious difference the curative effect in the two groups (P < 0.05). CONCLUSION: Combining exchange of cerebrospinal fluid with small dose of urokinase injection is an effective method for treating SAH, and it can improve the survival rate and life quality of SAH patients.
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Líquido Cefalorraquídeo , Drenaje/métodos , Hemorragia Subaracnoidea/terapia , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Adulto , Anciano , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the Cx32 mutation features and the clinical manifestations of Chinese patients with Charcot-Marie-Tooth disease(CMT). METHODS: Twenty-four of 65 unrelated CMT patients were selected for Cx32 mutation screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male transmission. The motor and sensory nerve conduction studies were performed in all probands and most of their affected family members to establish the clinical CMT1 ,CMT2 or CMT intermediate diagnosis. The presence of mutations in the coding region of Cx32 was detected by single-strand conformation polymorphism analysis combined with direct sequencing. RESULTS: We found 7 different point mutations in the coding region of Cx32 in a total of 7 families. All the patients were mildly to moderately affected with a clinical CMT1 or CMT intermediate diagnosis. The mutation Arg15Gln was inherited with X-linked recessive trait in family 1 involved in our study. The Arg75Trp mutation was detected in a family with X-linked dominant CMT and autosomal recessive nonsydromic hearing loss. The clinical phenotype of the Thr188Ala mutation was firstly reported. CONCLUSION: Seven different Cx32 point mutations were detected and the percentage of Chinese CMT families with Cx32 mutation is about 10% in our study. The inheritance model of CMT secondary to Cx32 mutation could be X-linked dominant, X-linked recessive or sporadic. Male patients are usually more severely affected than females with slower nerve conduction velocities. Cx32 mutation screening should be firstly performed in those CMT families without male-to-male transmission and CMT1A duplication.
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Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos X/genética , Conexinas/genética , Mutación Puntual , China/etnología , Femenino , Humanos , Masculino , Sistemas de Lectura Abierta/genética , Linaje , Proteína beta1 de Unión ComunicanteRESUMEN
OBJECTIVE: To set up a new grading system of intraventricular hemorrhage (IVH) and determine the value of predicting the probability of post-hemorrhagic hydrocephalus (PHH) in IVH. METHODS: We first modified the Graeb criteria, then compared the value of prediction for PHH assessed by the Graeb criteria with the modified Graeb criteria. One hundred and thirty one IVH patients were divided into two groups: the upper group (n = 67) and the lower group (n = 64). Gold standard of PHH was assessed by CT scan or by out-drainage. The diagnostic parameters such as sensitivity (SE), specificity (SP) were analyzed. In the cutoff point of SE and SP curves, diagnostic efficiency (DE), and Kappa value (K) were analyzed. The probability of PHH was estimated by binary logistic regressions. RESULTS: In all ventricular group, to Graeb criteria in the cutoff point, SE, SP, and K was 0.78, 0.84, and 0.60; and to modified Graeb criteria SE, SP, and K was 0.90, 0.84, and 0.74 respectively. The probability of PHH from point of 3-12 was 0.011, 0.032, 0.085, 0.212, 0.435, 0.689, 0.865, 0.949, 0.981, and 0.994 respectively according to modified Graeb criteria.
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Hemorragia Cerebral/complicaciones , Hidrocefalia/diagnóstico , Anciano , Hemorragia Cerebral/diagnóstico por imagen , Femenino , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To study the mutation feature of ganglioside-induced differentiation associated protein-1 (GDAP1) gene in Chinese Charcot-Marie-Tooth disease(CMT) patients. METHODS: Mutation analysis was carried out by use of polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) combined with DNA direct sequencing of the six exons and their flanking regions of GDAP1 gene in twenty-three CMT patients, including 8 probands of autosomal recessive CMT families and 15 sporadic patients. RESULTS: A compound heterozygous mutation A533G and A767G were unveiled in one autosomal recessive CMT kindred. The homozygous and heterozygous T507G were common SNPs in Chinese population. CONCLUSION: A533G and A767G of GDAP1 gene were new mutations firstly reported.