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Definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) relies on the examination of brain tissues for the pathological prion protein (PrPSc). Our previous study revealed that PrPSc-seeding activity (PrPSc-SA) is detectable in skin of sCJD patients by an ultrasensitive PrPSc seed amplification assay (PrPSc-SAA) known as real-time quaking-induced conversion (RT-QuIC). A total of 875 skin samples were collected from 2 cohorts (1 and 2) at autopsy from 2-3 body areas of 339 cases with neuropathologically confirmed prion diseases and non-sCJD controls. The skin samples were analyzed for PrPSc-SA by RT-QuIC assay. The results were compared with demographic information, clinical manifestations, cerebrospinal fluid (CSF) PrPSc-SA, other laboratory tests, subtypes of prion diseases defined by the methionine (M) or valine (V) polymorphism at residue 129 of PrP, PrPSc types (#1 or #2), and gene mutations in deceased patients. RT-QuIC assays of the cohort #1 by two independent laboratories gave 87.3% or 91.3% sensitivity and 94.7% or 100% specificity, respectively. The cohort #2 showed sensitivity of 89.4% and specificity of 95.5%. RT-QuIC of CSF available from 212 cases gave 89.7% sensitivity and 94.1% specificity. The sensitivity of skin RT-QuIC was subtype dependent, being highest in sCJDVV1-2 subtype, followed by VV2, MV1-2, MV1, MV2, MM1, MM1-2, MM2, and VV1. The skin area next to the ear gave highest sensitivity, followed by lower back and apex of the head. Although no difference in brain PrPSc-SA was detected between the cases with false negative and true positive skin RT-QuIC results, the disease duration was significantly longer with the false negatives [12.0 ± 13.3 (months, SD) vs. 6.5 ± 6.4, p < 0.001]. Our study validates skin PrPSc-SA as a biomarker for the detection of prion diseases, which is influenced by the PrPSc types, PRNP 129 polymorphisms, dermatome sampled, and disease duration.
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Síndrome de Creutzfeldt-Jakob , Enfermedades por Prión , Priones , Humanos , Priones/genética , Enfermedades por Prión/diagnóstico , Enfermedades por Prión/genética , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/genética , BiomarcadoresRESUMEN
BACKGROUND: Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower-extremity spasticity. Despite the identification of several HSP-related genes, many patients lack a genetic diagnosis. OBJECTIVES: The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4-associated HSP. METHODS: Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single-cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell-derived pyramidal neurons, and zebrafish. RESULTS: Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient-derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss-of-function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation. CONCLUSIONS: Our study confirms that loss-of-function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society.
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Paraplejía Espástica Hereditaria , Pez Cebra , Animales , Humanos , Ubiquinona/genética , Paraplejía Espástica Hereditaria/genética , Mutación/genética , Mutación Missense , Proteínas Mitocondriales/genéticaRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.
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Background: Mitochondrial myopathy is a group of diseases caused by abnormal mitochondrial structure or function. The mitochondrial myopathy impacts muscles of the whole body and exhibits variable symptoms. Respiratory muscle deficits deteriorate pulmonary function in patients with severe pneumonia. Case presentation: We report the case of a male patient with severe pneumonia-induced respiratory failure. He was abnormally dependent invasive ventilator-assisted ventilation after his condition had improved. Then we found abnormal ventilator waveform and a decline in muscle strength of him. Mitochondrial myopathy was ultimately confirmed by muscle pathological biopsy and body fluid genetic testing. Vitamin B complex, coenzyme Q10, Neprinol AFD, l-arginine, and MITO-TONIC were used to improve mitochondrial function and muscle metabolism. After treatment, discomfort associated with chest tightness, fatigue, cough, and sputum disappeared, and the patient was discharged. Conclusion: This case presented an uncommon cause of difficult weaning and extubation-acute onset of mitochondrial myopathy. Muscle biopsy and genetic testing of body fluid are essential for diagnosing mitochondrial myopathy. The A3243G mutation in the MT-TL1 gene of mitochondrial DNA contributes to pathogenesis of this case.
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The composition of the gut microbiota, including Akkermansia muciniphila (A. muciniphila), is altered in many neurological diseases and may be involved in the pathophysiological processes of Parkinson's disease (PD). A. muciniphila, a mucin-degrading bacterium, is a potential next-generation microbe that has anti-inflammatory properties and is responsible for keeping the body healthy. As the role of A. muciniphila in PD has become increasingly apparent, we discuss the potential link between A. muciniphila and various neurological diseases (including PD) in the current review.
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Enfermedades Autoinmunes , Microbioma Gastrointestinal , Enfermedad de Parkinson , Akkermansia , Enfermedades Autoinmunes/fisiopatología , Humanos , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/fisiopatología , VerrucomicrobiaRESUMEN
Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H2O2) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2. Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People's Hospital, China (approval No. 2018PHC081) on December 18, 2018.
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OBJECTIVE: To investigate the clinical and myopathological characteristics and desmin mutations in patients with desminopathy associated cardiomyopathy from 5 Chinese families. METHODS: Thirty-six individuals (18 male, 18 female) were from 4 autosomal dominant inherited families and 1 sporadic case. Nineteen patients manifested myopathy followed by cardiomyopathy; 13 patients presented with isolated cardiomyopathy; 1 patient had isolated myopathy; 3 patients died of cardiac diseases without detailed clinical information. Out of the 23 patients underwent electrocardiogram examinations, 20 patients showed kinds of abnormalities in cardiac conduction block. Echocardiogram revealed dilated cardiomyopathy in one case, hypertrophic cardiomyopathy in one case, and restrictive cardiomyopathy in two cases. Muscle specimens from 7 different patients were performed for histological, immunohistochemistry and ultrastructural examinations. All exons of the desmin gene were screened in 21 patients, 17 asymptomatic family individuals and 50 Chinese controls. RESULTS: Muscle biopsies revealed multiple proteins aggregated in muscle fibers, also supported by immunostaining and electroscopic examinations. Five novel heterogeneous mutations were identified in 4 families and one sporadic case. CONCLUSIONS: Novel mutations of desmin gene were linked with cardiomyopathy in patients from 5 Chinese families with desminopathy.
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Cardiomiopatías/genética , Desmina/genética , Mutación , Adolescente , Adulto , Pueblo Asiatico/genética , Cardiomiopatías/diagnóstico , Análisis Mutacional de ADN , Exones , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Neuronal intranuclear inclusion disease is a rare hereditary neurodegenerative disease characterized by localized eosinophilic intracytoplasmic inclusion bodies in cells of the nervous system and internal organs. This disorder is frequently missed or misdiagnosed, as there is significant heterogeneity of its clinical presentation. Recently, genetic sequencing has revealed complex links between neuronal intranuclear inclusion disease and other neurodegenerative diseases, potentially explaining the diversity of clinical manifestations. Herein, we describe the case of a 68-year-old male Chinese patient who was initially diagnosed with Parkinson's disease based on classic symptomatology and ¹²³I-metaiodobenzylguanidine scintigraphy results and was subsequently treated with oral methyldopa for 3 years. He developed a paroxysmal tic before he presented to our hospital for treatment after a convulsive seizure. Brain magnetic resonance imaging identified signal hyperintensity at the corticomedullary junction on diffusion-weighted imaging. Skin biopsy results and genetic testing confirmed a revised diagnosis of neuronal intranuclear inclusion disease. This report highlights that patients clinically diagnosed with Parkinson's disease may actually be in the early stages of neuronal intranuclear inclusion disease, suggesting that patients with suspected Parkinson's disease should also be screened for this disease.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Anciano , China , Humanos , Cuerpos de Inclusión Intranucleares , Masculino , Enfermedades Neurodegenerativas/diagnóstico , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
OBJECTIVE: To investigate the expression of PDCDS, Caspase-3, Bcl-2 and Bax in skeletal muscle of patients with mitochondrial encephalomyopathies with lactate acidosis and stroke like episodes (MELAS), limb-girdle type mitochondrial myopathy (LGMM) and chronic progressive external ophthalmoplegia (CPEO), and to explore the correlation between apoptosis and the pathogenesis of mitochondrial cytopathy. METHODS: Three patients with MELAS, 2 patients with LGMM and 6 patients with CPEO were enrolled, including eight males and three females, the diagnosis of MELAS, LGMM or CPEO was made on the basis of clinical manifestations, muscle biopsy specimen findings and a point mutation or a large-scale mitochondrial DNA deletion. Controls consisted of 11 muscle biopsy samples from subjects with no diagnostic findings (age and gender matched with patients'). Muscle biopsy was performed after obtaining the informed consent. The specimens were quickly frozen and transverse sections stained for hematoxylineosin, periodic acid Schiff reaction, oil red "0", modified Gomori trichrome, ATPase, NADH-TR, succinate dehydrogenase, cytochrome c oxidase, and nonspecific esterase. The expression of PDCD5, Caspase-3, Bcl-2 and Bax were detected by immunohistochemistry. The authors used the tissue slices of prostate or tonsil containing the target protein as positive control and PBS in place of these primary antibodies as negative control. RESULTS: PDCDS was highly expressed in some ragged red fibers in 2 patients with LGMM and 3 patients with CPEO. And it was also expressed in some capillary of patients with MELAS and LGMM. Caspase-3 was expressed in a few ragged red fibers in 1 patients with MELAS, 2 patients with LGMM and 1 patient with CPEO. And there was also expression in some capillary of both MELAS and LGMM. Bcl-2 staining showed a high expression in sarcoplasm of some ragged red fibers and atrophic fibers in 4 patients with MELAS, 2 patients with LGMM and 5 patients with CPEO, at the same time, it was weakly expressed in sarcoplasm of all type 2 muscle fibers and some small vessels of both patients and controls. There was no Bax immunoreactive fiber or vessel in MELAS, LGMM and CPEO patients. All of the above-mentioned proteins except Bcl-2 were negative in muscle fibers and vessels of controls. CONCLUSION: Abnormal regulation of apoptosis is involved in the pathophysiology of mitochondrial cytopathy. And PDCDS, Bcl-2 and Caspase-3 take part in regulation.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Músculo Esquelético/metabolismo , Proteínas de Neoplasias/metabolismo , Adolescente , Adulto , Apoptosis , Caspasa 3/metabolismo , Femenino , Humanos , Síndrome MELAS/metabolismo , Síndrome MELAS/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Adulto Joven , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Late-onset multiple acyl-coA dehydrogenase deficiency (MADD) is an autosomal recessive inherited metabolic disorder. It is still unclear about the muscle magnetic resonance image (MRI) pattern of the distal lower limb pre- and post-treatment in patients with late-onset MADD. This study described the clinical and genetic findings in a cohort of patients with late-onset MADD, and aimed to characterize the MRI pattern of the lower limbs. METHODS: Clinical data were retrospectively collected from clinic centers of Peking University People's Hospital between February 2014 and February 2018. Muscle biopsy, blood acylcarnitines, and urine organic acids profiles, and genetic analysis were conducted to establish the diagnosis of MADD in 25 patients. Muscle MRI of the thigh and leg were performed in all patients before treatment. Eight patients received MRI re-examinations after treatment. RESULTS: All patients presented with muscle weakness or exercise intolerance associated with variants in the electron transfer flavoprotein dehydrogenase gene. Muscle MRI showed a sign of both edema-like change and fat infiltration selectively involving in the soleus (SO) but sparing of the gastrocnemius (GA) in the leg. Similar sign of selective involvement of the biceps femoris longus (BFL) but sparing of the semitendinosus (ST) was observed in the thigh. The sensitivity and specificity of the combination of either "SO+/GA-" sign or "BFL+/ST-" sign for the diagnosis of late-onset MADD were 80.0% and 83.5%, respectively. Logistic regression model supported the findings. The edema-like change in the SO and BFL muscles were quickly recovered at 1 month after treatment, and the clinical symptom was also relieved. CONCLUSIONS: This study expands the clinical and genetic spectrums of late-onset MADD. Muscle MRI shows a distinct pattern in the lower limb of patients with late-onset MADD. The dynamic change of edema-like change in the affected muscles might be a potential biomarker of treatment response.
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Imagen por Resonancia Magnética/métodos , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Adolescente , Adulto , Biopsia/métodos , Carnitina/análogos & derivados , Carnitina/sangre , Flavoproteínas Transportadoras de Electrones/genética , Femenino , Músculos Isquiosurales/diagnóstico por imagen , Músculos Isquiosurales/metabolismo , Músculos Isquiosurales/patología , Humanos , Proteínas Hierro-Azufre/genética , Masculino , Persona de Mediana Edad , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/genética , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Accumulating evidence indicates that the aberrant re-entry of post-mitotic neurons into the G2/M phase of cell cycle and the resulting mitotic catastrophe may contribute to the pathogenesis of Alzheimer's disease. However, the cellular event that drives the differentiated neurons to abnormally enter G2/M phase remains elusive. Similarly, whether mitotic catastrophe is indeed one of the death pathways for differentiated neurons is not clear. Previous studies revealed that okadaic acid (OA), a phosphatase inhibitor that induces AD like pathological changes, evokes mitotic changes in neuroblastoma cells. In this study, we examined the in vivo effects of OA on cyclin B1 expression, the induction of mitosis, and subsequent mitotic catastrophe. We found that cyclin B1 expression in adult neurons was significantly increased after injecting OA into rat frontal cortex, which also increased tau protein phosphorylation. Interestingly, cyclin B1 and phosphorylated tau were well co-localized around the OA injection site, but were only partially co-localized in other brain regions. Staining with toluidine blue, Giemsa dye or propidium iodide revealed typical mitotic and mitotic catastrophe-like morphological changes with irregular arrangement of condensed chromatin and chromosome fibers in a few cells. Furthermore, the strong cyclin B1 staining in these cells suggests that cyclin B1 promoted G2 to M phase transition is required for the mitotic catastrophe. The detection of neuron-specific enolase in a portion of these cells demonstrated that at least part them are neuron. All together, our results suggest that the disturbance of the protein kinase-phosphatase system caused by OA is sufficient to induce neuronal cyclin B1 expression, force neurons into the mitotic phase of cell cycle, and cause mitotic catastrophe.
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Corteza Cerebral/efectos de los fármacos , Ciclina B/metabolismo , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Mitosis/efectos de los fármacos , Ácido Ocadaico/farmacología , Animales , Western Blotting/métodos , Ciclina B1 , Técnica del Anticuerpo Fluorescente/métodos , Masculino , Fosfopiruvato Hidratasa/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Proteínas tau/metabolismoRESUMEN
Recent evidence indicates that the aberrant neuronal expression of mitotic proteins in Alzheimer's disease (AD) brain may be related to AD pathological changes. To investigate whether the toxicity of beta-amyloid protein (Abeta) induces mitotic proteins expression in adult rat brain, we used immunohistochemical and integral optical density analytic method to analyze the adult rat brains, which had been injected with Abeta(25-35) into unilateral amygdala. Results showed that the levels of neurofibrillary tangle (NFT) related phosphorylated tau protein and apoptosis related protein Bax were increased in Abeta(25-35) injected rat brains, meanwhile the aberrantly expression of mitotic protein cyclin A and cyclin B1 was also detected at 7 d after operation, but the level of cyclin A decreased and cyclin B1 disappeared at 21 d. Immunofluorescence double labeling presented that cyclin B1 was partially co-localized with Bax or phosphorylated tau protein, whereas Bax and phosphorylated tau protein seldom co-localized. These results suggest that Abeta causes mitotic protein expression in adult brain neurons, which may die through apoptosis or may be affected by AD NFT-related tau phosphorylation.
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Amígdala del Cerebelo/fisiopatología , Péptidos beta-Amiloides/toxicidad , Ciclina A/metabolismo , Ciclina B1/metabolismo , Fragmentos de Péptidos/toxicidad , Proteína X Asociada a bcl-2/metabolismo , Proteínas tau/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Masculino , Neuronas/metabolismo , Fosforilación , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy (UCMD). METHODS: Clinical data of probands were collected and muscle biopsies of patients were analyzed. Exons of COL6A1, COL6A2 and COL6A3 were analyzed by direct sequencing. Mutations in COL6A1, COL6A2 and COL6A3 were identified in 8 patients. RESULTS: Among these mutations, 5 were novel [three in the triple helical domain (THD) and 2 in the second C-terminal (C2) domain]. We also identified five known missense or in-frame deletion mutations in THD and C domains. Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions. CONCLUSIONS: The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI, thereby providing useful information for the genetic counseling of UCMD patients.
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Colágeno Tipo VI/genética , Distrofias Musculares/genética , Mutación , Esclerosis/genética , Adolescente , Alelos , Sustitución de Aminoácidos , Biopsia , Niño , Preescolar , China , Codón , Femenino , Mutación del Sistema de Lectura , Humanos , Inmunohistoquímica , Masculino , Distrofias Musculares/diagnóstico , Mutación Missense , Polimorfismo de Nucleótido Simple , Esclerosis/diagnóstico , Eliminación de SecuenciaRESUMEN
OBJECTIVE: Periodic paralysis (PP) is one type of skeletal muscle channelopathies characterized by episodic attacks of weakness. It is usually classified into hyperkalemic periodic paralysis (HyperPP), hypokalemic periodic paralysis (HypoPP) and normokalemic periodic paralysis (NormoPP) based on the blood potassium levels. HypoPP is the most common type of these three and NormoPP is the rarest one. The aim of this study was to explore the clinical and genetic features of a Chinese family with normokalemic periodic paralysis (NormoKPP). METHOD: Clinical features of all patients in the family with NormoKPP were analyzed. Genomic DNA was extracted from peripheral blood leukocytes and amplified with PCR. We screened all 24 exons of SCN4A gene and then sequence analysis was performed in those who showed heteroduplex as compared with unaffected controls. RESULT: (1) Fifteen members of the family were clinically diagnosed NormoKPP, and their common features are: onset within infacy, episodic attacks of weakness, the blood potassium levels were within normal ranges, high sodium diet or large dosage of normal saline could attenuate the symptom. One muscle biopsy was performed and examination of light and electronic microscopy showed occasionally degenerating myofibers. (2) Gene of 12 patients were screened and confirmed mutations of SCN4A genes--c. 2111 T > C/p. Thr704Met. CONCLUSION: The study further defined the clinical features of patients with NormoKPP, and molecular genetic analysis found SCN4A gene c. 2111 T > C/p. Thr704Met point mutation contributed to the disease. In line with the autosomal dominant inheritance laws, this family can be diagnosed with periodic paralysis, and be provided with genetic counseling. And the study may also help the clinical diagnosis, guide treatment and genetic counseling of this rare disease in China.