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1.
Eur J Paediatr Neurol ; 36: 143-150, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34979476

RESUMO

This review focused on vaccination in children with movement disorders, including cerebral palsy and the movement disorders triggered by vaccination in children with and without neurological disabilities. The following clinical questions were addressed: 1) Can children with movement disorders be vaccinated? 2) Can vaccination trigger movement disorders in children without neurological disabilities? 3) Can vaccination trigger movement disorders in children with neurological disabilities? and 4) Is there any consensus of care concerning vaccination in children with movement disorders? Following the PRISMA reporting guidelines, 1096 records were identified and 34 relevant papers were included. No evidence that vaccinations are contraindicated for children with movement disorders was noticed. Several reports of neurological adverse events, including movement disorders in children without neurological disabilities after various types of vaccination, were found. The reporting rates were low, the causality was controversial, and patient outcomes were mostly favourable. There was limited (if any) evidence in our search that any vaccination leads to any movement disorder exacerbation. Finally, no generally accepted consensus or standards of care concerning vaccination in patients with movement disorders were found. In summary, we found few precautions for vaccination in this group of patients and concluded that general best practice guidelines for immunization should be followed. In addition, influenza and pneumococcal vaccines are recommended because they can reduce morbidity and mortality in individuals severely affected by movement restrictions.


Assuntos
Paralisia Cerebral , Vacinas contra Influenza , Influenza Humana , Transtornos dos Movimentos , Paralisia Cerebral/complicações , Criança , Humanos , Transtornos dos Movimentos/etiologia , Vacinação/efeitos adversos
2.
Eur Arch Otorhinolaryngol ; 279(1): 467-479, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34036422

RESUMO

INTRODUCTION: The facial nerve surgery belongs to the basic procedures during lateral skull base approaches. Its damage has serious medical and psychological consequences, and therefore mastery of reconstruction and correction techniques should belong to the repertoire of skull base surgeons. The goal of this study was to demonstrate usefulness of electromyographic follow-up in facial nerve reconstruction. MATERIAL AND METHODS: A total of 16 patients underwent hemihypoglossal-facial anastomosis between 2005 and 2017. Most of the primary lesions came from vestibular schwannoma surgery. All patients were examined with electromyography and scored according to the House-Brackmann and IOWA grading scales. Function of the tongue has been evaluated. RESULTS: Ten patients achieved definitive House-Brackmann grade 3 score (62.5%). We did not observe any association with the patient's age, previous irradiation and the etiology of the damage. Electromyography showed pathological spontaneous activity after the first surgery. Incipient regeneration potentials were detected in 4-17 months (average 7.6) and reached maximum in 6.5-18 months (average 16). Electromyographic assessment of the effect of tongue movement showed better mimic voluntary activity by swallowing or by moving the tongue up. There was no relationship between the start of activity and the interval to achieving maximal activity. CONCLUSION: Hemihypoglossal-facial nerve anastomosis is a safe procedure and it is an optimal solution for cases lacking a proximal stump or in the case of reconstruction in the second stage. Electromyography can predict initial reinnervation activity after reconstructive procedures. During subsequent follow-up it can help to discover insufficiently recovering patients, however clinical characteristics are crucial.


Assuntos
Nervo Facial , Paralisia Facial , Anastomose Cirúrgica , Nervo Facial/cirurgia , Humanos , Nervo Hipoglosso/cirurgia , Resultado do Tratamento
3.
Disabil Rehabil ; 44(22): 6668-6675, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34473588

RESUMO

PURPOSE: To obtain information on characteristics, management, current objective nutritional status and perception of nutritional status of children with cerebral palsy (CP) from healthcare professionals (HCPs) and caregivers. MATERIALS AND METHODS: A detailed survey of several items on eight main topics (general characteristics, motor function, comorbidities, therapies, anthropometry, feeding mode and problems and perceived nutritional status) was developed and tested for the study. Correlation between nutritional status and Gross Motor Function Classification System (GMFCS) levels was assessed using continuous variables (Z-scores for weight-for-age, height-for-age, weight-for-height, and body mass index-for-age), and categorical variables (being malnourished, stunted, or wasted). HCP and caregiver perceptions of the child's nutritional status as well as agreement between perceived and objective nutritional status and agreement between perceived nutritional status and concerns about the nutritional status were analyzed. RESULTS: Data were available for 497 participants from eight European countries. Poorer nutritional status was associated with higher (more severe) GMFCS levels. There was minimal agreement between perceived and objective nutritional status, both for HCPs and caregivers. Agreement between HCP and caregiver perceptions of the child's nutritional status was weak (weighted kappa 0.56). However, the concerns about the nutritional status of the child were in line with the perceived nutritional status. CONCLUSIONS: The risk of poor nutritional status is associated with more severe disability in children and adolescents with CP. There is a mismatch between HCP and caregiver perceptions of participants' nutritional status as well as between subjective and objective nutritional status. Our data warrant the use of a simple and objective screening tool in daily practice to determine nutritional status in children and adolescents with CP. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03499288 (https://clinicaltrials.gov/ct2/show/NCT03499288). IMPLICATIONS FOR REHABILITATIONUse of the ESPGHAN recommendations and simple screening tools in daily practice is needed to improve nutritional care for individuals with CP.Attention should be paid to the differences in the perception of nutritional status of individuals with CP between professionals and caregivers to improve appropriate referral for nutritional support.Objective measures rather than the professional's perception need to be used to define the nutritional status of individuals with CP.


Assuntos
Paralisia Cerebral , Desnutrição , Criança , Adolescente , Humanos , Estado Nutricional , Cuidadores , Desnutrição/diagnóstico , Inquéritos e Questionários
4.
Neuropsychiatr Dis Treat ; 12: 2367-2372, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27695335

RESUMO

Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism spectrum disorders (ASD). ASD were reported predominantly in congenital and early childhood forms of DM1. We describe dizygotic twin boys with ASD who were referred for routine laboratory genetic testing and in whom karyotyping, FMR1 gene testing, and single nucleotide polymorphism array analysis yielded negative results. The father of the boys was later diagnosed with suspected DM1, and testing revealed characteristic DMPK gene expansions in his genome as well as in the genomes of both twins and their elder brother, who also suffered from ASD. In accord with previous reports on childhood forms of DM1, our patients showed prominent neuropsychiatric phenotypes characterized especially by hypotonia, developmental and language delay, emotional and affective lability, lowered adaptability, and social withdrawal. The experience with this family and multiple literature reports of ASD in DM1 on the one side but the lack of literature data on the frequency of DMPK gene expansions in ASD patients on the other side prompted us to screen the DMPK gene in a sample of 330 patients with ASD who were first seen by a geneticist before they were 10 years of age, before the muscular weakness, which may signal DM1, usually becomes obvious. The absence of any DMPK gene expansions in this cohort indicates that targeted DMPK gene testing can be recommended only in ASD patients with specific symptoms or family history suggestive of DM1.

5.
J Hand Ther ; 29(1): 66-72; quiz 72, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26847322

RESUMO

STUDY DESIGN: Matched pair study. INTRODUCTION: Differences in hand-muscle strength/dexterity between dominant (DH) and non-dominant (NDH) hand in Charcot-Marie-Tooth disease (CMT) are not well understood. PURPOSE OF THE STUDY: To compare muscle strength/dexterity between DH and NDH and to correlate manual dexterity, strength and sensory function. PATIENTS AND METHODS: Thirty CMT patients were studied using functional muscle testing (FMT) and strength (dynamometry), dexterity (the Nine Hole Peg Test [NHPT]), and Jebsen-Taylor Hand Function [JTT]), and sensory function (the Nottingham Sensory Assessment [NSA]). RESULTS: Scores were worse for DH than NDH on FMT (p = 0.043) and NHPT (p = 0.014) but not on JTT (p = 0.098), handgrip strength (p = 0.710) or tripod pinch (p = 0.645). NSA did not correlate significantly with any tests (p's0.05). CONCLUSIONS: In CMT disease, DH appears more impaired than NDH in terms of function and dexterity. Greater muscle weakness in DH may also emerge as CMT progresses. LEVEL OF EVIDENCE: 3b.


Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Força da Mão/fisiologia , Destreza Motora/fisiologia , Adulto , Idoso , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Exame Neurológico , Adulto Jovem
6.
Cesk Patol ; 51(1): 34-40, 2015.
Artigo em Tcheco | MEDLINE | ID: mdl-25671360

RESUMO

Neurofibromatosis von Recklinghausen type 1 (NF1) is a multisystem, autosomal dominant hereditary neurocutaneous disease characterized by skin, central and peripheral nervous system , eyes , bone, endocrine, gastrointestinal and blood vessel wall involvement. It has an estimated frequency of 1 in 3000. Neurofibromatosis type 1 is caused by mutations in the large NF1 gene located on chromosome 17q11.2, encoding the cytoplasmic protein neurofibromin. It is expressed in multiple cell types but is highly expressed in Schwann cells, oligodendrocytes, neurons, astrocytes and leukocytes. Neurofibromin is known to act as a tumor suppressor via Ras-GTPase activation, which causes down-regulation of cellular signaling via the Ras/mitogen-activated protein kinase (MAPK) pathway. Failure of this function is associated with a tendency to form tumors which are histologically hamartomas as well as benign tumors. Tumors of the central nervous system include low-grade gliomas (pilocytic astrocytomas grade I), especially optic pathway gliomas. They are often clinically asymptomatic. Other intracranial tumors are in the brain stem and also elsewhere in the brain and spinal cord. Hydrocephalus may be a complication of NF1 gliomas or due to stenosis of the distal part of the aqueduct Silvii. Cutaneous and subcutaneous neurofibromas or plexiform neurofibromas are localized in the peripheral nervous system. Plexiform neurofibromas have a significant lifetime risk of malignancy. The clinical diagnosis of NF1 is defined by diagnostic criteria. The NF1 diagnosis is satisfied when at least two of the seven conditions are met. The method of direct DNA analysis of large NF1 gene (61 exons) is available. The results of studies of genotype - phenotype established few correlations. But predicting the disease by finding mutations is not currently possible. NF1 exhibits a wide range of variability of expression and complete penetrance, even within the same family. About half of cases are new mutations. The treatment of patients with neurofibromatosis is symptomatic. Central nervous system symptomatic low-grade gliomas are most often treated with chemotherapy. For plexiform neurofibromas surgical removal is currently the only treatment option.


Assuntos
Neurofibromatose 1 , Adulto , Feminino , Genes da Neurofibromatose 1 , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética
7.
PLoS One ; 9(9): e106509, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25184213

RESUMO

Improved drought tolerance is always a highly desired trait for agricultural plants. Significantly increased drought tolerance in Arabidopsis thaliana (Columbia-0) has been achieved in our work through the suppression of ESKMO1 (ESK1) gene expression with small-interfering RNA (siRNA) and overexpression of CBF genes with constitutive gene expression. ESK1 has been identified as a gene linked to normal development of the plant vascular system, which is assumed directly related to plant drought response. By using siRNA that specifically targets ESK1, the gene expression has been reduced and drought tolerance of the plant has been enhanced dramatically in the work. However, the plant response to external abscisic acid application has not been changed. ICE1, CBF1, and CBF3 are genes involved in a well-characterized plant stress response pathway, overexpression of them in the plant has demonstrated capable to increase drought tolerance. By overexpression of these genes combining together with suppression of ESK1 gene, the significant increase of plant drought tolerance has been achieved in comparison to single gene manipulation, although the effect is not in an additive way. Accompanying the increase of drought tolerance via suppression of ESK1 gene expression, the negative effect has been observed in seeds yield of transgenic plants in normal watering conditions comparing with wide type plant.


Assuntos
Adaptação Fisiológica/genética , Proteínas de Arabidopsis/genética , Secas , Estresse Fisiológico/genética , Ácido Abscísico/administração & dosagem , Arabidopsis , Proteínas de Arabidopsis/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , RNA Interferente Pequeno , Sementes , Transativadores/biossíntese
8.
Biomed Res Int ; 2014: 315952, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24987677

RESUMO

BACKGROUND: The aim of this study was to analyze complications of vestibular schwannoma (VS) microsurgery. MATERIAL AND METHODS: A retrospective study was performed in 333 patients with unilateral vestibular schwannoma indicated for surgical treatment between January 1997 and December 2012. Postoperative complications were assessed immediately after VS surgery as well as during outpatient followup. RESULTS: In all 333 patients microsurgical vestibular schwannoma (Koos grade 1: 12, grade 2: 34, grade 3: 62, and grade 4: 225) removal was performed. The main neurological complication was facial nerve dysfunction. The intermediate and poor function (HB III-VI) was observed in 124 cases (45%) immediately after surgery and in 104 cases (33%) on the last followup. We encountered disordered vestibular compensation in 13%, permanent trigeminal nerve dysfunction in 1%, and transient lower cranial nerves (IX-XI) deficit in 6%. Nonneurological complications included CSF leakage in 63% (lateral/medial variant: 99/1%), headache in 9%, and intracerebral hemorrhage in 5%. We did not encounter any case of meningitis. CONCLUSIONS: Our study demonstrates that despite the benefits of advanced high-tech equipment, refined microsurgical instruments, and highly developed neuroimaging technologies, there are still various and significant complications associated with vestibular schwannomas microsurgery.


Assuntos
Hemorragia Cerebral/epidemiologia , Neoplasias da Orelha/cirurgia , Doenças do Nervo Facial/epidemiologia , Cefaleia/epidemiologia , Microcirurgia/efeitos adversos , Neurilemoma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Doenças Vestibulares/cirurgia , Adolescente , Adulto , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Criança , Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/epidemiologia , Doenças do Nervo Facial/diagnóstico por imagem , Doenças do Nervo Facial/etiologia , Feminino , Cefaleia/diagnóstico por imagem , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/epidemiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Estudos Retrospectivos , Doenças Vestibulares/diagnóstico por imagem , Doenças Vestibulares/epidemiologia
9.
PLoS One ; 8(12): e82549, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349310

RESUMO

Myotonia congenita (MC) is a genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1) encoding the skeletal muscle chloride channel (ClC-1). Mutations of CLCN1 result in either autosomal dominant MC (Thomsen disease) or autosomal recessive MC (Becker disease). The ClC-1 protein is a homodimer with a separate ion pore within each monomer. Mutations causing recessive myotonia most likely affect properties of only the mutant monomer in the heterodimer, leaving the wild type monomer unaffected, while mutations causing dominant myotonia affect properties of both subunits in the heterodimer. Our study addresses two points: 1) molecular genetic diagnostics of MC by analysis of the CLCN1 gene and 2) structural analysis of mutations in the homology model of the human dimeric ClC-1 protein. In the first part, 34 different types of CLCN1 mutations were identified in 51 MC probands (14 mutations were new). In the second part, on the basis of the homology model we identified the amino acids which forming the dimer interface and those which form the Cl(-) ion pathway. In the literature, we searched for mutations of these amino acids for which functional analyses were performed to assess the correlation between localisation of a mutation and occurrence of a dominant-negative effect (corresponding to dominant MC). This revealed that both types of mutations, with and without a dominant-negative effect, are localised at the dimer interface while solely mutations without a dominant-negative effect occur inside the chloride channel. This work is complemented by structural analysis of the homology model which provides elucidation of the effects of mutations, including a description of impacts of newly detected missense mutations.


Assuntos
Canais de Cloreto/química , Canais de Cloreto/genética , Músculo Esquelético/metabolismo , Mutação , Miotonia Congênita/genética , Adolescente , Adulto , Canais de Cloreto/metabolismo , República Tcheca , Feminino , Humanos , Masculino , Modelos Moleculares , Mutação de Sentido Incorreto , Miotonia Congênita/diagnóstico , Fenótipo , Conformação Proteica , Multimerização Proteica , Adulto Jovem
10.
Transgenic Res ; 22(4): 725-36, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23271374

RESUMO

In sugar beet production, weed control is one of the most important and most expensive practices to ensure yield. Since glyphosate-resistant sugar beets are not yet approved for cultivation in the EU, little commercial experience exists with these sugar beets in Europe. Experimental field trials were conducted at five environments (Germany, Poland, 2010, 2011) to compare the effects of glyphosate with the effects of conventional weed control programs on the development of weeds, weed control efficiency and yield. The results show that the glyphosate weed control programs compared to the conventional methods decreased not only the number of herbicide applications but equally in magnitude decreased the dosage of active ingredients. The results also showed effective weed control with glyphosate when the weed covering was greater and sugar beets had a later growth stage of four true leaves. Glyphosate-resistant sugar beets applied with the glyphosate herbicide two or three times had an increase in white sugar yield from 4 to 18 % in comparison to the high dosage conventional herbicide systems. In summary, under glyphosate management sugar beets can positively contribute to the increasingly demanding requirements regarding efficient sugar beet cultivation and to the demands by society and politics to reduce the use of chemical plant protection products in the environment.


Assuntos
Beta vulgaris/genética , Produtos Agrícolas , Resistência a Herbicidas/genética , Controle de Plantas Daninhas , Beta vulgaris/crescimento & desenvolvimento , Europa (Continente) , Alemanha , Glicina/análogos & derivados , Glicina/farmacologia , Herbicidas , Humanos , Plantas Geneticamente Modificadas , Polônia , Glifosato
11.
Curr Biol ; 22(12): 1095-101, 2012 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-22608508

RESUMO

Life cycle adaptation to latitudinal and seasonal variation in photoperiod and temperature is a major determinant of evolutionary success in flowering plants. Whereas the life cycle of the dicotyledonous model species Arabidopsis thaliana is controlled by two epistatic genes, FLOWERING LOCUS C and FRIGIDA, three unrelated loci (VERNALIZATION) determine the spring and winter habits of monocotyledonous plants such as temperate cereals. In the core eudicot species Beta vulgaris, whose lineage diverged from that leading to Arabidopsis shortly after the monocot-dicot split 140 million years ago, the bolting locus B is a master switch distinguishing annuals from biennials. Here, we isolated B and show that the pseudo-response regulator gene BOLTING TIME CONTROL 1 (BvBTC1), through regulation of the FLOWERING LOCUS T genes, is absolutely necessary for flowering and mediates the response to both long days and vernalization. Our results suggest that domestication of beets involved the selection of a rare partial loss-of-function BvBTC1 allele that imparts reduced sensitivity to photoperiod that is restored by vernalization, thus conferring bienniality, and illustrate how evolutionary plasticity at a key regulatory point can enable new life cycle strategies.


Assuntos
Adaptação Biológica/fisiologia , Agricultura/métodos , Beta vulgaris/fisiologia , Evolução Biológica , Flores/fisiologia , Genes Reguladores/genética , Proteínas de Plantas/genética , Adaptação Biológica/genética , Sequência de Aminoácidos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Sequência de Bases , Beta vulgaris/genética , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Clonagem Molecular , Primers do DNA/genética , Flores/genética , Marcadores Genéticos/genética , Haplótipos/genética , Immunoblotting , Modelos Biológicos , Dados de Sequência Molecular , Fenótipo , Fotoperíodo , Filogenia , Estações do Ano , Seleção Genética , Alinhamento de Sequência , Análise de Sequência de DNA
12.
J Pediatr Surg ; 46(11): 2135-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22075345

RESUMO

BACKGROUND AND PURPOSE: Stimulation electromyography (sEMG) is useful in identifying the sphincter muscle (M) in patients with anorectal malformations (ARMs). This study evaluates the effect of anesthetic agents and M relaxants on sEMG findings. MATERIALS AND METHODS: Seventeen infants (10 boys and 7 girls) with a mean age of 6.3 months and mean body weight of 6.7 kg were included in a prospective randomized study. Anesthesia was induced by sevoflurane and opioids, and an epidural catheter was inserted caudally. Stimulation electromyography of levator ani M using 14 mA current was used, and latency and amplitude of the evoked compound M action potential (CMAP) were recorded. Patients were randomized into 2 groups. Group A received a local anesthetic epidurally, and sEMG was performed. Administration of the M relaxant and measurement of M response followed. In group B drug administration, sEMG and response measurement were performed after administration of M relaxant. RESULTS: Baseline CMAP was recorded in all patients. Average latency was 4.1 milliseconds, and average amplitude was 0.43 mV. In group A, the average latency was 4.0 milliseconds, and average amplitude was 0.65 mV. After administration of the M relaxant, the CMAP disappeared. In group B, no CMAP was observed immediately after administration of the M relaxant. CONCLUSION: Administration of the inhalational anesthetic, opioids, and local anesthetic did not influence the M response of M fibers in the levator ani M on sEMG and enables its localization during ARM reconstruction. Nondepolarizing M relaxation completely abolished the response. If M relaxant is necessary, cisatracurium is used. The most suitable method of anesthesia for ARM surgery appears to be inhalational anesthesia supplemented by opioids and epidural analgesia.


Assuntos
Canal Anal/anormalidades , Anestesia Epidural , Anestesia por Inalação , Anestesia Intravenosa , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Anestésicos Locais/farmacologia , Eletromiografia/métodos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Reto/anormalidades , Atracúrio/análogos & derivados , Atracúrio/farmacologia , Bupivacaína/análogos & derivados , Bupivacaína/farmacologia , Anormalidades do Sistema Digestório/diagnóstico , Eletrodos , Eletromiografia/instrumentação , Desenho de Equipamento , Potencial Evocado Motor/efeitos dos fármacos , Feminino , Humanos , Lactente , Recém-Nascido , Cuidados Intraoperatórios/métodos , Levobupivacaína , Masculino , Éteres Metílicos/farmacologia , Estudos Prospectivos , Tempo de Reação/efeitos dos fármacos , Sevoflurano , Sufentanil/administração & dosagem , Sufentanil/farmacologia
13.
Plant Mol Biol ; 74(1-2): 19-32, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20512402

RESUMO

The maize Activator/Dissociation (Ac/Ds) transposable element system was introduced into sugar beet. The autonomous Ac and non-autonomous Ds element excise from the T-DNA vector and integrate at novel positions in the sugar beet genome. Ac and Ds excisions generate footprints in the donor T-DNA that support the hairpin model for transposon excision. Two complete integration events into genomic sugar beet DNA were obtained by IPCR. Integration of Ac leads to an eight bp duplication, while integration of Ds in a homologue of a sugar beet flowering locus gene did not induce a duplication. The molecular structure of the target site indicates Ds integration into a double strand break. Analyses of transposase transcription using RT-PCR revealed low amounts of alternatively spliced mRNAs. The fourth intron of the transposase was found to be partially misspliced. Four different splice products were identified. In addition, the second and third exon were found to harbour two and three novel introns, respectively. These utilize each the same splice donor but several alternative splice acceptor sites. Using the SplicePredictor online tool, one of the two introns within exon two is predicted to be efficiently spliced in maize. Most interestingly, splicing of this intron together with the four major introns of Ac would generate a transposase that lacks the DNA binding domain and two of its three nuclear localization signals, but still harbours the dimerization domain.


Assuntos
Beta vulgaris/enzimologia , Beta vulgaris/genética , Transposases/genética , Zea mays/enzimologia , Zea mays/genética , Processamento Alternativo , Sequência de Bases , Primers do DNA/genética , Elementos de DNA Transponíveis , DNA Bacteriano/genética , DNA de Plantas/genética , Vetores Genéticos , Plantas Geneticamente Modificadas , Sítios de Splice de RNA , Nicotiana/enzimologia , Nicotiana/genética , Ativação Transcricional
14.
Neuromuscul Disord ; 19(11): 749-53, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19783145

RESUMO

Duchenne and Becker muscular dystrophies (DMD/BMD) are associated with mutations in the DMD gene. We determined the mutation status of 47 patients with dystrophinopathy without deletion or duplication in the DMD gene by screening performed by reverse transcription-PCR, protein truncation test, and DNA sequencing. We describe three patients with a mutation creating a premature termination codon (p.E55X, p.E1110X, and p.S3497PfsX2) but with a mild phenotype, which present three different ways of rescuing the DMD phenotype. In one patient we detected the insertion of a repetitive sequence AluYa5 in intron 56, which led to skipping of exon 57. Further, using quantitative analysis of DMD mRNA carrying various mutated alleles, we examine levels of mRNA degradation due to nonsense mediated mRNA decay. The quantity of dystrophin mRNA is different depending on the presence of a mutation leading to a premature termination codon, and position of the analysed mRNA region with respect to its 5' end or 3' end. Average relative amounts of DMD mRNAs carrying a premature termination codon is 48% and 17%, when using primers amplifying the 5' and 3' cDNA regions, respectively.


Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Fenótipo , Mutação Puntual , Sequência de Bases , República Tcheca , Análise Mutacional de DNA/métodos , Distrofina/metabolismo , Éxons , Feminino , Humanos , Masculino , Dados de Sequência Molecular , RNA Mensageiro/metabolismo
15.
Pediatr Neurol ; 41(2): 127-30, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19589462

RESUMO

Described here is the phenotypical expression of a novel LMNA mutation c.1157 G>T in a Czech patient with an early-onset form of Emery-Dreifuss muscular dystrophy. The mutation predicts aberrant splicing. Now 21 years old, the patient has had slowly progressing muscle dystrophy since the age of one and early contractures of elbows. He is the only family member affected. Even though the dystrophy typically affects the heart as well, in the present case these signs are not yet expressed.


Assuntos
Lamina Tipo A/genética , Distrofia Muscular de Emery-Dreifuss/genética , Mutação de Sentido Incorreto , Idade de Início , Análise Mutacional de DNA , Articulação do Cotovelo , Humanos , Lordose/genética , Masculino , Fenótipo , Escoliose/genética , Adulto Jovem
16.
Am J Med Genet A ; 149A(7): 1365-74, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19514047

RESUMO

Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the 3' UTR of the DMPK gene. A length exceeding 50 CTG triplets is pathogenic. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. We report on the identification of multiple patients with different patterns of CCG and CTC interruptions in the DMPK CTG repeat tract that display unique intergenerational instability. In patients bearing interrupted expanded alleles, the location of the interruptions changed dramatically between generations and the repeats tended to contract. The phenotype for these patients corresponded to the classical form of the disease, but in some cases without muscular dystrophy and possibly with a later onset than expected. Symptomatic patients bearing interrupted intermediate length repeat tracts were also identified, although the role of the interruptions in their phenotype remains unclear. The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions.


Assuntos
Deleção de Genes , Proteínas Serina-Treonina Quinases/genética , Repetições de Trinucleotídeos/genética , Adulto , Sequência de Bases , Estudos de Casos e Controles , Análise Mutacional de DNA , Família , Feminino , Frequência do Gene , Instabilidade Genômica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miotonina Proteína Quinase , Linhagem , Adulto Jovem
17.
Neuro Endocrinol Lett ; 28(6): 761-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18063947

RESUMO

OBJECTIVES: The aim of the study was to investigate the relationship of serum levels of neuron-specific enolase, anti-vimentin IgG, and anti-vimentin IgM antibodies in patients with neurofibromatosis type 1 and associated tumors (optic glioma, and plexiform neurofibroma). METHODS: Measurement of neuron-specific enolase and anti-vimentin antibodies were performed in 131 children and adolescents (67 males, mean age 10 years, range 4-19 years; 64 females, mean age 11 years, range 1-20 years) with three different forms of neurofibromatosis type 1 and in control group of 40 individuals (20 males, mean age 9 years, range 1-19 years and 20 females, mean age 12 years, range 3-18 years). RESULTS: Anti-vimentin IgG, IgM antibodies and NSE showed similar ability to distinguish between neurofibromatosis type 1 and tumors associated with neurofibromatosis type 1. (AUC=0.57, AUC=0.52 and AUC=0.59 respectively). NSE showed better diagnostic efficiency (AUC=0.68) than the anti-vimentin IgG and anti-vimentin IgM. (AUC=0.63 and AUC=0.56 respectively). Anti-vimentin IgG and IgM antibodies showed higher sensitivity (87.5% and 87.2%) at the cut off value than the NSE (54%). On the contrary, NSE showed higher specificity at the cut off value than both the anti-vimentin IgG and IgM (71% vs. 22.5% and 16% respectively). CONCLUSIONS: Anti-vimentin IgG and IgM and neuron-specific enolase are relevant markers in investigation of the patients with neurofibromatosis type 1 and associated tumors.


Assuntos
Neoplasias do Sistema Nervoso Central/imunologia , Neurofibroma Plexiforme/imunologia , Neurofibromatose 1/imunologia , Glioma do Nervo Óptico/imunologia , Fosfopiruvato Hidratase/sangue , Neoplasias Cutâneas/imunologia , Vimentina/imunologia , Adolescente , Adulto , Formação de Anticorpos/imunologia , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso Central/complicações , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Neurofibroma Plexiforme/sangue , Neurofibroma Plexiforme/complicações , Neurofibromatose 1/sangue , Neurofibromatose 1/complicações , Glioma do Nervo Óptico/sangue , Glioma do Nervo Óptico/complicações , Sensibilidade e Especificidade , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/complicações , Estatísticas não Paramétricas
18.
Am J Ophthalmol ; 143(4): 663-71, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17239335

RESUMO

PURPOSE: To confirm and define a molecular basis for a case of mucolipidosis type IV (ML IV) with an extremely atypical phenotype pattern. DESIGN: Observational case report of a patient with ML IV with disease progression restricted to ocular symptoms. METHODS: Complete ophthalmologic and neurologic examination. Ultrastructural examination of white blood cells, skin, conjunctiva, and corneal epithelium. The MCOLN1 gene was sequenced from cDNA and the proportion of splicing variants were assessed by quantitative allele-specific polymerase chain reaction. RESULTS: Absence of any neurological abnormalities. Retinal pathologic features were the main cause of visual disability: low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years. Ultrastructural examination showed storage lysosomes filled with either concentric membranes or lucent precipitate in corneal and conjunctive epithelia and in vascular endothelium. Cultured fibroblasts were free of any autofluorescence. Sequencing of the MCOLN1 gene identified compound heterozygosity for D362Y and A-->T transition leading to the creation of a novel donor splicing site and a 4-bp deletion from exon 13 at the mRNA level. Both normal and pathologic splice forms were detected in skin fibroblasts and leukocytes, with the normal form being more abundant. CONCLUSIONS: The case of this patient with ML IV is unique and is characterized by a curious lack of generalized symptoms. In this patient, the disorder was limited to the eyes and appeared without the usual psychomotor deterioration. The resulting phenotype is the mildest seen to date.


Assuntos
Processamento Alternativo/genética , Doenças da Córnea/genética , Mucolipidoses/genética , Mutação , Degeneração Retiniana/genética , Canais de Cátion TRPM/genética , Criança , Doenças da Túnica Conjuntiva/genética , Doenças da Túnica Conjuntiva/patologia , Doenças da Córnea/patologia , Análise Mutacional de DNA , Eletrorretinografia , Células Epiteliais/ultraestrutura , Epitélio Corneano/ultraestrutura , Feminino , Fibroblastos/ultraestrutura , Humanos , Leucócitos/ultraestrutura , Lisossomos/genética , Lisossomos/ultraestrutura , Mucolipidoses/patologia , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Degeneração Retiniana/patologia , Pele/ultraestrutura , Canais de Potencial de Receptor Transitório
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