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1.
Neurol Sci ; 43(6): 3683-3694, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35044558

RESUMEN

OBJECTIVE: Meige syndrome (MS) is cranial dystonia, including bilateral eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). Up to now, the pathogenic genes of MS and BSP are still unclear. METHODS: We performed Sanger sequencing of GNAL, TOR1A, TOR2A, THAP1, and REEP4 exons on 78 patients, including 53 BSP and 25 MS and 96 healthy controls. RESULTS: c.845G > C[R282P] of TOR1A, c.629delC[p.Gly210AlafsTer60] of TOR2A, c.1322A > G[N441S] of GNAL, c.446G > A[R149Q], and c.649C > T[R217C] of REEP4 were identified and predicated as deleterious probably damaging variants. Three potential alterations of splicing variants of TOR1A and TOR2A were identified in patients. The frequencies of TOR1A rs1435566780 and THAP1 rs545930392 were higher in patients than in controls. CONCLUSIONS: TOR1A rs1435566780 (c.*16G > C(G > A)) and THAP1 rs545930392 (c.192G > A[K64K]) may contribute to the etiology of MS and BSP. Other identified rare mutations predicted as deleterious probably damaging need further confirmation. Larger MS and BSP cohorts and functional studies will need to be performed further to elucidate the association between these genes and the diseases.


Asunto(s)
Blefaroespasmo , Distonía , Trastornos Distónicos , Síndrome de Meige , Proteínas Reguladoras de la Apoptosis/genética , Blefaroespasmo/genética , Proteínas de Unión al ADN/genética , Distonía/genética , Trastornos Distónicos/genética , Pruebas Genéticas , Humanos , Síndrome de Meige/genética , Proteínas de Transporte de Membrana/genética , Chaperonas Moleculares/genética
2.
J Clin Lab Anal ; 34(8): e23324, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32274857

RESUMEN

BACKGROUND: Mutations in the FBXO7 gene can cause a rare chromosomal recessive neurodegenerative disease, Parkinsonian-pyramidal syndrome (PPS). Patients with this syndrome mainly show early-onset Parkinson's syndrome. Here, we present a Chinese family with infantile-onset PPS caused by FBXO7 mutations. METHODS: The clinical phenotypes and medical records of the proband and his family members were collected. The proband, his sibling, and his parents underwent whole-exome sequencing (WES) by next-generation sequencing. RESULTS: The proband and his sibling had a typical PPS phenotype with onset during infancy. WES identified compound heterozygous variants in the FBXO7 gene, including a nonsense mutation, p. Trp134*, and a splicing mutation, IVS5-1G > A, which were shared by both siblings and inherited from each of the parents. These variants have not been reported in literatures or databases. According to the American College of Medical Genetics and Genomics guidelines, the p. Trp134* and IVS5-1G > A mutations were classified as pathogenic variants. CONCLUSIONS: We report a case of siblings in a Chinese family with infantile-onset PPS caused by FBXO7 gene mutations determined by WES. These findings will contribute to the in-depth study of the pathogenesis of PPS among patients with FBXO7 gene mutations.


Asunto(s)
Blefaroespasmo , Proteínas F-Box/genética , Mutación/genética , Enfermedad de Parkinson Secundaria , Adulto , Pueblo Asiatico/genética , Blefaroespasmo/genética , Blefaroespasmo/patología , Encéfalo/patología , Niño , Preescolar , China , Análisis Mutacional de ADN , Femenino , Globo Pálido/patología , Humanos , Masculino , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/patología , Linaje , Hermanos , Secuenciación del Exoma
3.
J Neurochem ; 144(2): 118-127, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29134665

RESUMEN

Parkinson disease (PD) is, without doubt, a burden on modern society as the prevalence increases significantly with age. Owing to this growing number of PD cases, it is more critical than ever to understand the pathogenic mechanisms underlying PD to identify therapeutic targets. The discovery of genetic mutations associated with PD and parkinsonism paves the way toward this goal. Even though, familial forms of the disease represent the minority of PD cases and some forms are so rare that there are only a few affected families, the research on the associated genes is invaluable. Recent additions to PARK mutations are those in PARK15 that encodes the F-box protein O-type 7 (FBXO7). In this review, we highlight the recent research on FBXO7, which advances our knowledge of the etiopathological pathways and fills unexpected gaps therein, justifying the dedicated study of rare variants of PD.


Asunto(s)
Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Animales , Blefaroespasmo/genética , Globo Pálido , Humanos , Ratones , Enfermedad de Parkinson Secundaria/genética
4.
BMC Med Genet ; 17(1): 93, 2016 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-27919237

RESUMEN

BACKGROUND: Cervical dystonias have a variable presentation and underlying etiology, but collectively represent the most common form of focal dystonia. There are a number of known genetic forms of dystonia (DYT1-27); however the heterogeneity of disease presentation does not always make it easy to categorize the disease by phenotype-genotype comparison. CASE PRESENTATION: In this report, we describe a 53-year-old female who presented initially with hand tremor following a total hip arthroplasty. The patient developed a mixed hyperkinetic disorder consisting of chorea, dystonia affecting the upper extremities, dysarthria, and blepharospasm. Whole exome sequencing of the patient revealed a novel heterozygous missense variant (Chr11(GRCh38): g.26525644C > G; NM_031418.2(ANO3): c.702C > G; NP_113606.2. p.C234W) in exon 7 in the ANO3 gene. CONCLUSIONS: ANO3 encodes anoctamin-3, a Ca+2-dependent phospholipid scramblase expressed in striatal-neurons, that has been implicated in autosomal dominant craniocervical dystonia (Dystonia-24, DYT24, MIM# 615034). To date, only a handful of cases of DYT-24 have been described in the literature. The complex clinical presentation of the patient described includes hyperkinesias, complex motor movements, and vocal tics, which have not been reported in other patients with DYT24. This report highlights the utility of using clinical whole exome sequencing in patients with complex neurological phenotypes that would not normally fit a classical presentation of a defined genetic disease.


Asunto(s)
Blefaroespasmo/genética , Canales de Cloruro/genética , Disartria/genética , Distonía/genética , Hipercinesia/genética , Tics/genética , Abdomen/diagnóstico por imagen , Secuencia de Aminoácidos , Anoctaminas , Blefaroespasmo/complicaciones , Blefaroespasmo/patología , Disartria/complicaciones , Disartria/patología , Distonía/complicaciones , Distonía/patología , Electrofisiología , Exones , Femenino , Heterocigoto , Humanos , Hipercinesia/complicaciones , Hipercinesia/patología , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Missense , Linaje , Polimorfismo Genético , Alineación de Secuencia , Tics/complicaciones , Tics/patología
5.
J Neurol Neurosurg Psychiatry ; 87(4): 420-4, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25904812

RESUMEN

BACKGROUND: Adult-onset isolated focal dystonia may present with various phenotypes including blepharospasm and cervical dystonia. Although inherited in an autosomal dominant manner with a markedly reduced penetrance, environmental factors are considered important in disease penetrance and expression. We observed a marked variation by latitude in the reports of the frequency of patients with blepharospasm relative to those with cervical dystonia; we hypothesised that sun exposure is an environmental risk factor for the development of blepharospasm in genetically susceptible individuals. METHODS: From published clinic cohorts and epidemiological reports, the ratio of the number of cases of blepharospasm to cervical dystonia (phenotype case ratio) at each study site was analysed with regard to latitude and measures of annual insolation. Meta-regression analyses of the phenotype case ratio to these environmental factors were performed. RESULTS: The phenotype case ratio in 15 eligible study sites over 41° of latitude demonstrated a statistically significant inverse association with latitude (p=0.0004, R(2)=53.5%). There were significant positive associations between the phenotype case ratio and quarter-one (January-March) insolation (p=0.0005, R(2)=53%) and average annual insolation (p=0.003, R(2)=40%). CONCLUSION: The increase in the blepharospasm: cervical dystonia case ratio with decreasing latitude and increasing insolation suggests that sunlight exposure is an environmental risk factor for the development of blepharospasm (rather than cervical dystonia) in individuals genetically susceptible to adult-onset dystonia.


Asunto(s)
Blefaroespasmo/etiología , Luz Solar/efectos adversos , Blefaroespasmo/epidemiología , Blefaroespasmo/genética , Ambiente , Predisposición Genética a la Enfermedad , Geografía , Humanos
6.
Ann Neurol ; 73(4): 459-71, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23526723

RESUMEN

OBJECTIVE: To date, 3 rare missense mutations in the SNCA (α-synuclein) gene and the more frequent duplications or triplications of the wild-type gene are known to cause a broad array of clinical and pathological symptoms in familial Parkinson disease (PD). Here, we describe a French family with a parkinsonian-pyramidal syndrome harboring a novel heterozygous SNCA mutation. METHODS: Whole exome sequencing of DNA from 3 patients in a 3-generation pedigree was used to identify a new PD-associated mutation in SNCA. Clinical and pathological features of the patients were analyzed. The cytotoxic effects of the mutant and wild-type proteins were assessed by analytical ultracentrifugation, thioflavin T binding, transmission electron microscopy, cell viability assay, and caspase-3 activation. RESULTS: We identified a novel SNCA G51D (c.152 G>A) mutation that cosegregated with the disease and was absent from controls. G51D was associated with an unusual PD phenotype characterized by early disease onset, moderate response to levodopa, rapid progression leading to loss of autonomy and death within a few years, marked pyramidal signs including bilateral extensor plantar reflexes, occasionally spasticity, and frequently psychiatric symptoms. Pathological lesions predominated in the basal ganglia and the pyramidal tracts and included fine, diffuse cytoplasmic inclusions containing phospho-α-synuclein in superficial layers of the cerebral cortex, including the entorhinal cortex. Functional studies showed that G51D α-synuclein oligomerizes more slowly and its fibrils are more toxic than those of the wild-type protein. INTERPRETATION: We have identified a novel SNCA G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features.


Asunto(s)
Ácido Aspártico/genética , Blefaroespasmo/genética , Salud de la Familia , Glicina/genética , Mutación Missense/genética , Enfermedad de Parkinson Secundaria/genética , alfa-Sinucleína/genética , Adulto , Anciano , Anciano de 80 o más Años , Amiloide/metabolismo , Amiloide/ultraestructura , Blefaroespasmo/patología , Caspasa 3/metabolismo , Análisis Mutacional de ADN , Relación Dosis-Respuesta a Droga , Femenino , Francia , Globo Pálido/patología , Humanos , Masculino , Persona de Mediana Edad , Neuroblastoma/patología , Proteínas de Neurofilamentos/metabolismo , Enfermedad de Parkinson Secundaria/patología
7.
Artículo en Inglés | MEDLINE | ID: mdl-38076033

RESUMEN

Background: Genetic factors have been implicated in the pathogenesis of blepharospasm (BSP), a dystonia characterized by excessive blinking and involuntary eyelid closure. Previous research identified a co-segregating deleterious TOR2A variant (GRCh38/hg38, NC_000009.12: g.127733410G>A, NM_001085347.3:c.568C>T, p. Arg190Cys) in three subjects with BSP and three carriers within a multi-generation pedigree. Other TOR2A variants have been reported in patients with dystonia. Methods: Sanger sequencing was used to screen a cohort of 307 subjects with isolated BSP or BSP-plus dystonia affecting additional anatomical segments (BSP+). We also utilized computational tools to uniformly assess the deleteriousness and potential pathogenicity of previously reported TOR2A variants. Results: There were no highly deleterious TOR2A variants in the coding or contiguous splice site regions of TOR2A within our cohort of 307 subjects. Discussion: Highly deleterious variants in TOR2A are rare in patients with BSP/BSP+ phenotypes. Highlights: Over 300 patients with BSP were screened for variants in TOR2A, a TOR1A (DYT1) homologue. No highly deleterious variants were identified in our cohort. The role of TOR2A in BSP and other forms of dystonia remains indeterminant.


Asunto(s)
Blefaroespasmo , Distonía , Trastornos Distónicos , Humanos , Blefaroespasmo/genética , Distonía/genética , Trastornos Distónicos/genética , Chaperonas Moleculares/genética , Linaje
8.
Clin Neurol Neurosurg ; 224: 107549, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36502650

RESUMEN

18q- Syndrome is a rare chromosomic syndrome where neurological involvement is scarcely described. Movement disorders are rare and only one case with dystonia was described. In our paper, we describe the second report of a patient with 18q- Syndrome, blepharospasm, and dystonic tremor of his right hand and hyperthyroidism instead of hypothyroidism.


Asunto(s)
Blefaroespasmo , Trastornos de los Cromosomas , Distonía , Trastornos Distónicos , Humanos , Distonía/complicaciones , Distonía/genética , Temblor/genética , Blefaroespasmo/complicaciones , Blefaroespasmo/genética , Trastornos Distónicos/complicaciones , Trastornos Distónicos/genética
9.
Mol Biol Rep ; 39(2): 1517-26, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21611747

RESUMEN

Parkinsonian pyramidal syndrome, also named pallido-pyramidal syndrome (PKPS), is the combination of early-onset progressive Parkinsonism with pyramidal tract signs. FBXO7, an F-box protein, is a component of modular E3 ubiquitin protein ligases called SCFs (SKP1, cullin, F-box proteins), which functions in phosphorylation-dependent ubiquitination. FBXO7 mutations cause autosomal recessive, early-onset PKPS. Here we report the molecular cloning and characterization of two isoforms of FBXO7 cDNA from pigs. The encoded FBXO7 protein displays a very high homology to human FBXO7 with an amino acid identity of 90%. Phylogenetic analysis demonstrated that porcine FBXO7 is closely related to other mammalian FBXO7 proteins. Furthermore, the genomic structure of the porcine FBXO7 gene was determined. The intron-exon structure is similar to that of the human FBXO7 gene. The promoter sequence for the porcine FBXO7 gene was also identified. A recognition site for miR-301a was found in the 3'UTR region of porcine FBXO7. Investigating the genetic variation in the porcine FBXO7 gene revealed a missense A/G SNP in exon 5. The A/G SNP results in a substitution of an asparagine to a serine residue (N269S). Using a radiation hybrid map the FBXO7 gene was mapped to pig chromosome 5. Real-time quantitative RT-PCR analysis revealed that FBXO7 mRNA is differentially expressed in many tissues and organs, and that FBXO7 transcript can be detected early in embryo development.


Asunto(s)
Blefaroespasmo/genética , Modelos Animales de Enfermedad , Proteínas F-Box/genética , Enfermedad de Parkinson Secundaria/genética , Filogenia , Polimorfismo de Nucleótido Simple/genética , Sus scrofa/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Análisis por Conglomerados , Cartilla de ADN/genética , Componentes del Gen , Globo Pálido , Datos de Secuencia Molecular , Isoformas de Proteínas/genética , Mapeo de Híbrido por Radiación , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Homología de Secuencia
10.
Acta Neurol Taiwan ; 21(3): 99-107, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23196729

RESUMEN

Genetic factors have been known to contribute to familial Parkinson's disease (PD), one of the most common neurodegenerative disorders. During the past decade, six of eleven causative genes linked to familial forms of PD have been identified to associate with autosomal-recessive young-onset Levodopa-responsive parkinsonism. Among these genes, mutations in Parkin, PINKl and DJ-1 are associated with a relatively typical parkinsonian phenotype with sustained treatment response to Levodopa. However, mutations inATP13A2, PLA2G6 and FBX07 are often associated with rapidly progressive parkinsonism and with additional features including pyramidal signs, cognitive decline and loss of sustained Levodopa responsiveness.Clarifying the phenotypes of each of these autosomal-recessive parkinsonian-pyramidal syndromes and understanding the mechanism ot these causative gene products might illuminate the pathogenesis of dopaminergic neuronal degeneration also in the common forms of PD.


Asunto(s)
Blefaroespasmo/genética , Mutación , Enfermedad de Parkinson Secundaria/genética , Trastornos Parkinsonianos/genética , Edad de Inicio , Blefaroespasmo/complicaciones , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/genética , Proteínas F-Box/genética , Salud de la Familia , Globo Pálido , Fosfolipasas A2 Grupo VI/genética , Humanos , Enfermedad de Parkinson Secundaria/complicaciones , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/tratamiento farmacológico , Fenotipo , ATPasas de Translocación de Protón/genética
12.
Parkinsonism Relat Disord ; 88: 62-67, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34144229

RESUMEN

BACKGROUND: Mutations in the F-box protein 7 (FBXO7) gene is one of the genetic causes of early-onset Parkinson's disease, which usually presents as autosomal recessive early-onset parkinsonian-pyramidal syndrome (PPS). Herein, we report a Chinese PPS family with a novel FBXO7 homozygous mutation. METHODS: Clinical data of the proband and his affected sister manifesting as early-onset parkinsonism combined with pyramidal signs were collected. DNAs of the two affected siblings, an unaffected sibling and their unaffected mother were isolated. Whole-exome sequencing (WES) was performed for the proband. After bioinformatic analysis, targeted variants were validated by Sanger sequencing in the family members available for DNAs. RESULTS: The proband began to walk unsteadily at 30-year-old and developed mild parkinsonism and stiffness in both lower extremities 4 years later. His older sister also manifested as early-onset parkinsonism with stiffness in both lower limbs and postural instability. Both the proband and his older sister carried a novel homozygous FBXO7 mutation in exon 7 (c.1034G > C, p. R345P). The homozygous mutation co-segregated with disease in this pedigree. The mutation located at a highly conserved amino acid residue in the F-box domain, which was predicted to be damaging in silico. CONCLUSIONS: Our study expands the mutational spectrum of autosomal recessive early-onset Parkinson's disease (PARK15) caused by FBXO7 mutations.


Asunto(s)
Blefaroespasmo/genética , Blefaroespasmo/fisiopatología , Proteínas F-Box/genética , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/fisiopatología , Adulto , Edad de Inicio , China , Femenino , Globo Pálido/fisiopatología , Humanos , Masculino , Mutación , Linaje , Secuenciación del Exoma
13.
J Mol Neurosci ; 70(9): 1370-1375, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32424513

RESUMEN

Blepharospasm (BSP) is a neurological movement disorder. Coffee consumption has been found to have a protective effect against BSP. BSP and apraxia of eyelid opening are particularly common among patients with PD. The CYP1A2 rs762551 and ADORA2A rs5760423 variants have been previously marginally associated with the risk of PD and are also implicated in caffeine metabolism pathways. The aim of the present study was to evaluate the effect of the CYP1A2 rs762551 and ADORA2A rs5760423 variants on BSP. A Southeastern European Caucasian (SEC) cohort of 206 BSP patients and 206 healthy controls was genotyped for rs762551 and rs5760423. CYP1A2 rs762551 was associated with a decreased BSP risk in the dominant (OR (95% CI) 0.62 (0.41-0.92), p = 0.017), log-additive (OR (95% CI) 0.68 (0.51-0.92), p = 0.011), and co-dominant modes (for the CC genotype OR (95% CI) 0.49 (0.25-0.93), p = 0.038). We provide preliminary evidence that CYP1A2 rs762551 is associated with BSP. Further studies and replication of our results are needed.


Asunto(s)
Blefaroespasmo/genética , Citocromo P-450 CYP1A2/genética , Polimorfismo de Nucleótido Simple , Receptor de Adenosina A2A/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
14.
Parkinsonism Relat Disord ; 80: 142-147, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33002721

RESUMEN

BACKGROUND: Mutations in the F-box protein 7 (FBXO7) gene result in autosomal recessive parkinsonism. This usually manifests as early-onset parkinsonian-pyramidal syndrome but patients exhibit high phenotypic variability. Here we describe the findings of a Yemeni family with two novel FBXO7 mutations. METHODS: Clinical data and DNA were available for three siblings with early-onset parkinsonism together with their parents and three unaffected siblings. A targeted next generation sequencing panel was used to screen the proband for mutations in 14 genes known to cause a parkinsonian disorder. In addition, SNCA, PARK2, PINK1, and PARK7 were screened for copy number variants. RESULTS: The proband carried two novel compound heterozygous FBXO7 mutations: a missense mutation in exon 1 (p.G39R; c.115G > A) and a frameshift mutation in exon 5 (p.L280fs; c.838del). The mutations segregated with disease in the family with the exception of a potentially pre-symptomatic individual whose age was below the age of onset in two of their three affected siblings. P.G39R occurred at a highly conserved amino acid residue and both mutations were predicted to be deleterious in silico. In contrast to most reported families, the phenotype in this pedigree was consistent with clinically typical Parkinson's disease (PD) with a lack of pyramidal signs and good response to dopaminergic therapy. CONCLUSIONS: Our study expands the phenotype associated with FBXO7 to include early-onset PD and broadens the list of causative mutations. These data suggest that FBXO7 should be included in clinical genetic testing panels for PD, particularly in patients with early onset or a recessive inheritance pattern.


Asunto(s)
Proteínas F-Box/genética , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/fisiopatología , Adulto , Edad de Inicio , Anciano , Blefaroespasmo/genética , Blefaroespasmo/fisiopatología , Femenino , Globo Pálido/fisiopatología , Humanos , Masculino , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/fisiopatología , Linaje , Yemen
15.
J Mol Neurosci ; 70(9): 1376-1384, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32424512

RESUMEN

Lysophosphatidic acid (LPA), a ubiquitous phospholipid, plays a crucial role in the pathogenesis and pathophysiological process of neurological diseases, which constitute the pathological course after cerebral ischemia. Nevertheless, the molecular mechanisms associated with the pathogenic roles of LPA remain elusive. In this study, we evaluated the expression of the liver X receptor (LXR) and nuclear factor kappa B (NFκB) by Western blotting, quantified the levels of IL-1ß, IL-6, TNF-α, and LPA by ELISA, and evaluated apoptosis and infarct by TUNEL (terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling) and TTC (triphenyltetrazolium chloride) staining respectively in Sprague-Dawley (SD) rats after middle cerebral artery occlusion (MCAO). The levels of LPA, an extracellular signaling molecule, increased after ischemia and caused neurological injury effect, decreased the expression level of LXR, and increased the expression level of inflammatory factors (IL-1ß, IL-6, and TNF-α) via the NFκB signaling pathway. This elevated LPA-induced pathological process is one of the pathological reactions associated with ischemic brain injury. We present a direct or indirect connection between LPA and LXR in the pathophysiological process. In conclusion, we speculate that the inhibition of LPA generation and administration of LXR agonist may be explored as potential cerebral infarction treatment strategies.


Asunto(s)
Blefaroespasmo/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Lisofosfolípidos/metabolismo , Animales , Blefaroespasmo/genética , Encéfalo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
16.
Mov Disord ; 24(4): 613-6, 2009 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-19202559

RESUMEN

We studied the influence of the rs1182 polymorphism of the TOR1A gene on the risk of dystonia spread in two representative cohorts of patients presenting with primary blepharospasm (BSP), one from Italy and the other from the United States of America. The relationship between rs1182 polymorphism and spread was estimated by Kaplan-Meier survival curves and Cox proportional hazard regression models adjusted by age and sex, age of BSP onset. In both series, patients carrying the T allele (G/T or T/T) in the rs1182 polymorphism were more likely to have dystonia spread as compared with the homozygous carriers of the common G allele. The comparable findings obtained in two independent cohorts support a genetic contribution to BSP spread.


Asunto(s)
Blefaroespasmo/genética , Predisposición Genética a la Enfermedad , Chaperonas Moleculares/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Blefaroespasmo/mortalidad , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Estados Unidos
17.
J Mol Neurosci ; 67(3): 472-476, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30656493

RESUMEN

Blepharospasm (BSP) is a sub-phenotype of focal dystonia. A few genetic risk factors are considered to be implicated in the risk of developing BSP. There is recent evidence, based on results from GWAS and meta-analyses, to suggest that arylsulfatase G (ARSG), and more specifically rs11655081, is implicated in focal dystonia. The aim of the present study was to evaluate the effect of rs11655081 ARSG on BSP. A Greek cohort, which consisted of 206 BSP patients and an equal number of healthy controls, was genotyped for rs11655081. Only a marginal trend for the association between rs11655081 and the risk of BSP was found in the over-dominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 0.64 (0.38-1.07), p = 0.088]. It is rather unlikely that rs11655081 across ARSG is a major genetic risk contributor for BSP.


Asunto(s)
Arilsulfatasas/genética , Blefaroespasmo/genética , Polimorfismo de Nucleótido Simple , Humanos
18.
Parkinsonism Relat Disord ; 64: 315-318, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30956059

RESUMEN

INTRODUCTION: Blepharospasm is a common type of focal dystonia that involves involuntary eyelid spasms and eye closure. In familial cases, an autosomal dominant pattern of inheritance is noted with reduced penetrance. Few genes have been associated with the disease including GNAL and CIZ1. A whole exome sequencing study published lately suggested TOR2A and REEP4 as potential candidate genes. METHODS: Sanger sequencing of GNAL, CIZ1, TOR2A and REEP4 exons including exon-intron boundaries in 132 patients diagnosed primarily with blepharospasm and/or Meige's syndrome. RESULTS: All variants detected in GNAL, CIZ1 and TOR2A seem to be benign. Sequencing of REEP4 revealed the presence of two nonsynonymous SNVs, one potential splice site variant and one indel all predicted to be damaging by in silico algorithms. CONCLUSION: Sequencing REEP4 in larger blepharospasm cohorts and functional studies will need to be performed to further elucidate the association between REEP4 and the disease.


Asunto(s)
Blefaroespasmo/genética , Trastornos Distónicos/genética , Síndrome de Meige/genética , Adolescente , Adulto , Anciano , Femenino , Pruebas Genéticas , Humanos , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Análisis de Secuencia de ADN , Adulto Joven
19.
Neuromolecular Med ; 21(1): 68-74, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30519954

RESUMEN

A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. The effect of rs6265 on BSP was evaluated. 206 patients with BSP and 206 healthy controls were recruited and genotyped for the rs6265. We also performed a meta-analysis, by pooling our results with those from previous studies. A significant effect of rs6265 on the risk of BSP was found in the dominant model of inheritance [odds ratio (OR) (95% confidence interval (CI) 1.52 (1.01-2.29), p = 0.044]. Mutational load analysis of rs6265 in the risk of BSP using the ORG revealed that higher load of the "A" allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.48; 95% CI 1.00-2.19). Finally, pooled results from the meta-analysis revealed that the rs6265 is associated with an increased risk of BSP in the dominant model [OR 1.26; 95% CI 1.02-1.55, pz = 0.03]. Also, higher load of the "A" allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.26; 95% CI 1.04-1.53). The present study provides additional evidence to the existing knowledge concerning the contribution of the rs6265 BDNF on the risk of developing BSP. While the pathophysiology and genetic susceptibility in BSP and focal dystonia are only partially understood, it seems that BDNF and rs6265 may constitute one essential risk factor that is heavily involved.


Asunto(s)
Blefaroespasmo/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Factor Neurotrófico Derivado del Encéfalo/fisiología , Estudios de Casos y Controles , Hibridación Genómica Comparativa , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Factores de Riesgo
20.
Medicina (B Aires) ; 68(4): 318-24, 2008.
Artículo en Español | MEDLINE | ID: mdl-18786893

RESUMEN

Benign essential blepharospasm is characterized by abnormal repetitive movements of lid closure and spasm of the orbiculari oculi muscles. Modern theories postulate that this movement disorder originates by abnormal processing of afferent information with further disintegration of the sensorimotor neural program at central levels of the nervous system all of which is seen as dystonic movements in genetically susceptible people. Different investigations including neuroimagin, genetic and neurophysiological studies have discovered new findings on what structures are involved and how this abnormal movement is generated. Among these research is noteworthy the study of electrically elicited blink reflex. It consists of three responses called non-nociceptive (R1), nociceptive (R2) and ultranociceptive (R3). Such blink reflexes, mostly the ultranociceptive response (R3), seem to be very useful to understand more deeply the pathophysiology of this focal dystonia, to perform the functional endophenotyping and to do a more appropriate follow-up of this complex neurological problem.


Asunto(s)
Blefaroespasmo/fisiopatología , Parpadeo/fisiología , Espasmo Hemifacial/fisiopatología , Blefaroespasmo/genética , Humanos , Aparato Lagrimal/fisiopatología
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