Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 284
Filtrar
1.
Pathobiology ; 86(4): 190-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31238314

RESUMO

OBJECTIVE: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. METHODS: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. RESULTS: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53-10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05). CONCLUSION: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.


Assuntos
Ferredoxina-NADP Redutase/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único , Alelos , Pai , Feminino , Ácido Fólico/metabolismo , Genótipo , Homocisteína/metabolismo , Homocistinúria/genética , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Mães , Espasticidade Muscular/genética , Defeitos do Tubo Neural/fisiopatologia , Polimorfismo de Fragmento de Restrição , Gravidez , Transtornos Psicóticos/genética , Tunísia
2.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936323

RESUMO

Sacral dural arteriovenous fistulas (SDAVFs) are rare, constituting no more than 10% of all spinal dural fistulas. They are most commonly fed by the lateral sacral artery (LSA), a branch of the internal iliac artery (IIA). Catheterization of this vessel requires either a crossover at the aortic bifurcation in cases of right femoral access or retrograde catheterization from the ipsilateral common femoral artery. We present the case of a 79-year-old man with tethered cord syndrome and a symptomatic SDAVF fed by two feeders from the left LSA. Spinal diagnostic angiography was made exceptionally challenging by an aorto-bi-iliac endograft, and selective catheterization of the left IIA was not possible. The patient could not undergo surgery due to multiple comorbidities, therefore embolization was considered the best approach. The procedure was carried out through a transradial access (TRA) with Onyx and n-butyl cyanoacrylate. The SDAVF was successfully treated and the patient made a full neurological recovery.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Embolização Terapêutica , Defeitos do Tubo Neural/diagnóstico , Paraparesia/diagnóstico por imagem , Recuperação de Função Fisiológica/fisiologia , Sacro/irrigação sanguínea , Idoso , Angiografia , Malformações Vasculares do Sistema Nervoso Central/fisiopatologia , Malformações Vasculares do Sistema Nervoso Central/terapia , Embolização Terapêutica/métodos , Humanos , Masculino , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/terapia , Paraparesia/etiologia , Paraparesia/fisiopatologia , Guias de Prática Clínica como Assunto , Sacro/diagnóstico por imagem , Resultado do Tratamento , Andadores
3.
Ital J Pediatr ; 45(1): 37, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867013

RESUMO

BACKGROUND: Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. METHODS: We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. RESULTS: There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308). CONCLUSION: Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.


Assuntos
Deficiência de Ácido Fólico/genética , Predisposição Genética para Doença/epidemiologia , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Carbono/metabolismo , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Ferredoxina-NADP Redutase/genética , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/epidemiologia , Marcadores Genéticos/genética , Genótipo , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Antígenos de Histocompatibilidade Menor/genética , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/fisiopatologia , Razão de Chances , Gravidez , Valores de Referência
4.
Birth Defects Res ; 111(5): 261-269, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30708397

RESUMO

BACKGROUND: Additional congenital anomalies have often been found in patients with neural tube defect (NTD). We aimed to find out the clinical features, short term prognosis, treatment approaches, and systemic anomalies of NTD patients in the Konya region. METHOD: A total of 186 newborn babies with NTD were retrospectively included in the study and all were assessed in detail for congenital anomalies and clinical features. RESULTS: When the application month of the patients was examined, it was seen that the most frequent month was July. Of 186 babies, 101(54.3%) had meningomyelocele, 53 (28.5%) had meningocele, 13 (7.0%) had encephalocele, 16 (8.6%) had spina bifida occulta, and 4 (2.1%) had anencephaly. Of these patients, 97 (52.2%) were male and 89 (47.8%) were female. Hydrocephalus was an almost constant finding and was found in 140 (75.3%) patients. 51 (27.4%) patients had congenital heart disease (CHD). The most common CHD was atrial septal defect 22.3%. Orthopedic anomaly was detected in 51 (27.4%) patients, nephrological anomaly was found in 47 (25.3%) of the cases, congenital hypothyroidism was diagnosed in 14 (7.5%) patients with NTD. The mortality rate of patients diagnosed with NTD was 7.5%. The rates of premature delivery and consanguinity between parents were higher in patients with NTD. CONCLUSIONS: Our results indicate that at least one congenital anomaly is also present in about two-thirds of newborn babies with NTD, and these anomalies significantly increase their morbidity and mortality. All newborn babies with NTD should be screened for additional congenital anomalies and evaluated with more organized, multidisciplinary methods.


Assuntos
Malformações do Sistema Nervoso/etiologia , Defeitos do Tubo Neural/complicações , Anencefalia , Anormalidades Congênitas/etiologia , Consanguinidade , Encefalocele , Feminino , Cardiopatias Congênitas , Humanos , Recém-Nascido , Masculino , Defeitos do Tubo Neural/mortalidade , Defeitos do Tubo Neural/fisiopatologia , Gravidez , Nascimento Prematuro , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Turquia/epidemiologia
5.
Acta Orthop Traumatol Turc ; 53(2): 160-164, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30718132

RESUMO

We report the surgical treatment course of a 4-year-old girl with congenital scoliosis, diastematomyelia and double adjacent hemivertebrae. She had a lumbar curve with an apparent pelvic obliquity. Simultaneous excision of double segmented sequential hemivertebra at the L3-L4 level and fusion with short-segment instrumentation was performed via a posterior approach. Intraoperative radiographs revealed satisfactory curve correction and 0° pelvic obliquity. Following the excision of double adjacent hemivertebrae, three adjacent nerve roots were placed in one intervertebral foramen bilaterally. Nevertheless, no neurological deficit was developed, and the patient was able to ambulate with a brace at day one. Pelvic balance and deformity correction were maintained with no implant failure at the fifth year follow-up. Excision of two ipsilateral adjacent hemivertebra and short-segment posterior fusion performed via posterior-only approach simultaneously is an effective, safe, and less invasive technique for the treatment of the described case.


Assuntos
Vértebras Lombares , Defeitos do Tubo Neural , Pelve , Escoliose , Fusão Vertebral , Braquetes , Pré-Escolar , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/terapia , Osteotomia/métodos , Pelve/diagnóstico por imagem , Pelve/fisiopatologia , Radiografia/métodos , Estudos Retrospectivos , Escoliose/congênito , Escoliose/diagnóstico , Escoliose/cirurgia , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Resultado do Tratamento
6.
Eur J Anaesthesiol ; 36(3): 175-184, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30507621

RESUMO

BACKGROUND: Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE: The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN: A retrospective cohort study. SETTING: Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION: Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS: Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. CONCLUSION: Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.


Assuntos
Anestesia/métodos , Fetoscopia/métodos , Histerectomia/métodos , Monitorização Intraoperatória/métodos , Defeitos do Tubo Neural/cirurgia , Analgésicos Opioides/administração & dosagem , Anestesia/efeitos adversos , Anestesia/tendências , Estudos de Coortes , Feminino , Fetoscopia/efeitos adversos , Fetoscopia/tendências , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Histerectomia/efeitos adversos , Histerectomia/tendências , Monitorização Intraoperatória/tendências , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/fisiopatologia , Bloqueadores Neuromusculares/administração & dosagem , Gravidez , Estudos Retrospectivos , Adulto Jovem
7.
Pan Afr Med J ; 34: 151, 2019.
Artigo em Francês | MEDLINE | ID: mdl-32110267

RESUMO

Tethered cord syndrome is a spectrum of neurological symptoms due to a constant or intermittent axial traction of the terminal cone of the spinal cord, fixed in abnormal caudal position. It is a rare congenital lesion whose symptoms can be observed only in adulthood. We report the case of a 10-year-old boy with tethered cord syndrome discovered due to bladder and anal incontinence and confirmed by lumbosacral magnetic resonance imaging. He underwent neurosurgical release of the terminal cone by posterior approach. Evolution was marked by improvement of sphincteric disorders. This case study has been followed by a literature review on this subject. This case study highlights the role of magnetic resonance imaging (MRI) in the diagnosis of this disorder.


Assuntos
Imagem por Ressonância Magnética/métodos , Defeitos do Tubo Neural/diagnóstico , Criança , Incontinência Fecal/etiologia , Humanos , Masculino , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/cirurgia , Incontinência Urinária/etiologia
8.
PLoS One ; 13(11): e0206212, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30427877

RESUMO

INTRODUCTION: Neural tube defects are the major causes of fetal loss and considerable disabilities in infants. Currently, there is no significant research on the incidence of Neural tube defects in the Tigray region of Ethiopia. OBJECTIVE: To determine the incidence and clinical pattern of the Neural Tube Defects. METHODS: A hospital-based cross-sectional study was conducted from October 2016 to June 2017. All pregnancy outcomes were examined for any externally visible birth defects and neurological integrity by trained midwives under the supervision of senior obstetrics and gynecology and a neurosurgeon. Data were collected using a survey tool to collect maternal and newborn demographic data and a checklist developed to capture newborns with Neural Tube Defects. Data were analyzed using SPSS version 20. The prevalence of NTDs was calculated per 10,000 births. RESULT: Out of the 14,903 births during the study period, a total of 195 infants were born afflicted with Neural Tube Defects. The burden of infants with anencephaly and spina bifida was 66.4 and 64.4 per 10, 000 births, respectively. The overall incidence rate of NTDs in this study was 131 per 10, 000 births of which 23% were liveborn and 77% were stillborn. The highest burden of Neural Tube Defects was observed in Adigrat Hospital from Eastern Zone of Tigray (174 per 10,000 births) and Lemlem Karl Hospital from Southern Zone of Tigray (304 per 10,000 births) compared to Kahsay Abera Hospital from Western Zone (72.8 per 10,000 births) and Sihul Hospital from North Western Zone of Tigray (69.8 per 10,000 births). CONCLUSION AND RECOMMENDATION: Assuming that the non folic acid preventable rate should be 5 per 10,000 births, our prevalence rate is 131 per 10,000 births, and then we have a rate or an epidemic that is 26 times what it should be. This just emphasizes the urgency to implement effective programs to get all women of reproductive age to have adequate folic acid to prevent all of folic acid-preventable spina bifida and anencephaly, which would prevent 96% (125/130) of spina bifida and anencephaly in the Tigray Provence.


Assuntos
Ácido Fólico/metabolismo , Defeitos do Tubo Neural/epidemiologia , Disrafismo Espinal/epidemiologia , Adulto , Estudos Transversais , Etiópia/epidemiologia , Feminino , Ácido Fólico/administração & dosagem , Hospitais , Humanos , Recém-Nascido , Nascimento Vivo , Defeitos do Tubo Neural/dietoterapia , Defeitos do Tubo Neural/fisiopatologia , Vigilância da População , Gravidez , Resultado da Gravidez , Disrafismo Espinal/dietoterapia , Disrafismo Espinal/fisiopatologia , Adulto Jovem
9.
Int J Dev Biol ; 62(9-10): 641-645, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30378389

RESUMO

Neural tube defects are common and serious birth defects in which the brain and/or spinal cord are exposed outside the body. Supplementation of foods with folic acid, an essential vitamin, is linked to a lower risk of neural tube defects; however, the mechanisms by which folic acid influence neural tube defect risk are unclear. Our research seeks to identify the basic cellular roles of known folic acid metabolism genes during morphogenesis using the roundworm Caenorhabditis elegans (C. elegans) as a simple model system. Here, we used live imaging to characterize defects in embryonic development when mel-32 is depleted. mel-32 is an essential folic acid metabolism gene in C. elegans and a homolog to the mammalian enzyme serine hydroxymethyltransferase (Shmt). Disruption of mel-32 resulted in a doubling or tripling of cell cycle lengths and a lack of directed cell movement during embryogenesis. However, the order of cell divisions, as determined by lineage analysis, is unchanged compared to wild type embryos. These results suggest that mel-32/Shmt is required for normal cell cycle lengths in C. elegans.


Assuntos
Caenorhabditis elegans/fisiologia , Ciclo Celular , Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário , Ácido Fólico/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Defeitos do Tubo Neural/fisiopatologia , Animais , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/enzimologia , Embrião não Mamífero/citologia , Glicina Hidroximetiltransferase/genética , Morfogênese
10.
Eur J Med Genet ; 61(12): 783-789, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30391508

RESUMO

Heterozygous gain of function mutations in the ZIC1 gene have been described with syndromic craniosynostosis, variable cerebral or cerebellar abnormalities and mild to moderate developmental delay. Deletion of chromosome 3q25.1 including both adjacent ZIC1 and ZIC4 genes have been described as a cause of variable cerebellar abnormalities including Dandy-Walker malformation. We report two siblings presenting with neonatal microcephaly, agenesis of the corpus callosum, brachycephaly with reduced volume of the posterior fossa, cerebellar and pons hypoplasia, scoliosis and tethered cord (closed neural tube defect). One of the siblings had apparent partial rhombencephalosynapsis. Trio analysis of exome sequencing data revealed a novel heterozygous frameshift mutation in ZIC1 at the end of exon 3 in one sibling and was confirmed by Sanger sequencing in both children. The mutation was not detected in DNA of both parents, which suggests parental gonadal mosaicism. We show that expression of the mutant allele leads to synthesis of a stable abnormal transcript in patient cells, without evidence for nonsense-mediated decay. Craniosynostosis was not present at birth, which explains why ZIC1 mutations were not initially considered. This severe brain malformation indicates that premature closure of sutures can be independent of the abnormal brain development in subjects with pathogenic variants in ZIC1.


Assuntos
Craniossinostoses/genética , Malformações do Desenvolvimento Cortical/genética , Microcefalia/genética , Fatores de Transcrição/genética , Adolescente , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/fisiopatologia , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Craniossinostoses/fisiopatologia , Feminino , Mutação da Fase de Leitura , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical/fisiopatologia , Microcefalia/fisiopatologia , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/fisiopatologia , Fenótipo , Escoliose/genética , Escoliose/fisiopatologia
11.
Dev Biol ; 444 Suppl 1: S193-S201, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098999

RESUMO

Folate deficiency has been known to contribute to neural tube and neural crest defects, but why these tissues are particularly affected, and which are the molecular mechanisms involved in those abnormalities are important human health questions that remain unanswered. Here we study the function of two of the main folate transporters, FolR1 and Rfc1, which are robustly expressed in these tissues. Folate is the precursor of S-adenosylmethionine, which is the main donor for DNA, protein and RNA methylation. Our results show that knockdown of FolR1 and/or Rfc1 reduced the abundance of histone H3 lysine and DNA methylation, two epigenetic modifications that play an important role during neural and neural crest development. Additionally, by knocking down folate transporter or pharmacologically inhibiting folate transport and metabolism, we observed ectopic Sox2 expression at the expense of neural crest markers in the dorsal neural tube. This is correlated with neural crest associated defects, with particular impact on orofacial formation. By using bisulfite sequencing, we show that this phenotype is consequence of reduced DNA methylation on the Sox2 locus at the dorsal neural tube, which can be rescued by the addition of folinic acid. Taken together, our in vivo results reveal the importance of folate as a source of the methyl groups necessary for the establishment of the correct epigenetic marks during neural and neural crest fate-restriction.


Assuntos
Deficiência de Ácido Fólico/fisiopatologia , Crista Neural/metabolismo , Fatores de Transcrição SOXB1/fisiologia , Animais , Embrião de Galinha , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/genética , Repressão Epigenética/genética , Repressão Epigenética/fisiologia , Epigenômica , Receptor 1 de Folato , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Histonas/metabolismo , Humanos , Tubo Neural/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/fisiopatologia
12.
Birth Defects Res ; 110(14): 1129-1138, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30120883

RESUMO

BACKGROUND: Worldwide, Neural tube defects (NTDs) are considered as major clinical problems imposing a huge socio-economic burden for both affected individuals and their families. In India, the prevalence of Neural tube defects is significantly high. This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India. METHODS: We enrolled 62 consecutive mothers with NTDs foetuses as cases and their corresponding age matched 73 mothers with healthy babies as controls (genetic power has been calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR: rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to find out association with NTDs. RESULTS: Genotype and allele frequency analysis of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11; 95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value ≤ 0.0001). CONCLUSION: In conclusion, it can be stated that, rs1801133 was associated with neural tube defects risk in patients from the eastern part of India and it might be counted as a molecular marker for evaluating the susceptibility of NTDs.


Assuntos
Ácido Fólico/genética , Ácido Fólico/metabolismo , Defeitos do Tubo Neural/genética , Adulto , Alelos , Antígenos de Superfície/genética , Antígenos de Superfície/fisiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Glutamato Carboxipeptidase II/genética , Glutamato Carboxipeptidase II/fisiologia , Homocisteína/análise , Homocisteína/sangue , Humanos , Índia/epidemiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/fisiologia , Pessoa de Meia-Idade , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/fisiopatologia , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/fisiologia
13.
J Neurosci ; 38(20): 4762-4773, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29712790

RESUMO

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation.SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy.


Assuntos
Anticonvulsivantes/toxicidade , Defeitos do Tubo Neural/fisiopatologia , Tubo Neural/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Transdução de Sinais/fisiologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Movimento Celular , Proliferação de Células , Feminino , Glutamatos/fisiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Placa Neural/citologia , Placa Neural/crescimento & desenvolvimento , Tubo Neural/crescimento & desenvolvimento , Defeitos do Tubo Neural/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Ácido Valproico/toxicidade , Xenopus laevis
14.
Medicine (Baltimore) ; 97(16): e0489, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29668630

RESUMO

RATIONALE: Neurenteric cysts, are rare benign tumors of the central nervous system that are mostly located in the spinal cord and predominantly seen in male children although adult form of the disorder also occurs. The etiology and treatment of this disorder is still a matter of debate. Our case further throws more light on the pathogenesis and treatment of this disorder. PATIENT CONCERNS: A 4-year-old boy presented with 5-month history of cervical lordosis and bilateral lower extremity pain that progressed to his abdomen and upper body. The pain was general, recurrent, non-persistent and progressive in nature with no paralysis. The pain was aggravated by trunk stretching and relieved when he assumed opisthotonos position so he preferred sleeping in this position at night. DIAGNOSES: Magnetic resonance imaging (MRI) revealed a cystic lesion at the thoracolumbar spine with tethering of spinal cord and cervical lordosis. INTERVENTIONS: He was operated on successfully and the cervical lordosis and pain resolved. OUTCOMES: The child recovered well with no tumor recurrence and massive improvement of his life. LESSONS: The gold standard treatment for this disorder is surgery although the precise surgical approach is still a matter of debate. We are of the view that surgical approach should be individualized and aim at total excision of the cyst.


Assuntos
Lordose , Defeitos do Tubo Neural , Procedimentos Neurocirúrgicos/métodos , Medula Espinal , Pré-Escolar , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Lordose/diagnóstico , Lordose/etiologia , Imagem por Ressonância Magnética/métodos , Masculino , Defeitos do Tubo Neural/complicações , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/cirurgia , Dor/diagnóstico , Dor/etiologia , Medula Espinal/anormalidades , Medula Espinal/fisiopatologia , Medula Espinal/cirurgia , Resultado do Tratamento
16.
Hum Genet ; 137(3): 195-202, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29423651

RESUMO

Neural tube defects (NTDs), which include spina bifida and anencephaly, are the second most common form of human structural congenital malformations. While it is well established that SHROOM3 plays a pivotal role in the complex morphogenetic processes involved in neural tube closure (NTC), the underlying genetic contributions of SHROOM gene family members in the etiology of human NTDs remain poorly understood. Herein, we systematically investigated the mutation patterns of SHROOM1-4 in a Chinese population composed of 343 NTD cases and 206 controls, using targeted next-generation sequencing. Functional variants were further confirmed by western blot and the mammalian two-hybrid assays. Loss of function (LoF) variants were identified in SHROOM3. We observed 1.56 times as many rare [minor allele frequency (MAF) < 0.01] coding variants (p = 2.9 × 10-3) in SHROOM genes, and 4.5 times as many rare D-Mis (deleterious missense) variants in SHROOM2 genes in the NTD cases compared with the controls. D-Mis variants of SHROOM2 (p.A1331S; p.R1557H) were confirmed by Sanger sequencing, and these variants were determined to have profound effects on gene function that disrupted their binding with ROCK1 in vitro. These findings provide genetic and molecular insights into the effects of rare damaging variants in SHROOM2, indicating that such variants of SHROOM2 might contribute to the risk of human NTDs. This research enhances our understanding of the genetic contribution of the SHROOM gene family to the etiology of human NTDs.


Assuntos
Anencefalia/genética , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Defeitos do Tubo Neural/genética , Feto Abortado , Anencefalia/fisiopatologia , China , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Mutação com Perda de Função/genética , Masculino , Proteínas de Membrana/química , Proteínas dos Microfilamentos/química , Defeitos do Tubo Neural/fisiopatologia , Disrafismo Espinal/genética , Disrafismo Espinal/fisiopatologia
18.
Clin Genet ; 93(4): 870-879, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29205322

RESUMO

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.


Assuntos
Anencefalia/genética , Epistasia Genética , Defeitos do Tubo Neural/genética , Disrafismo Espinal/genética , Anencefalia/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Estudos de Associação Genética , Humanos , Masculino , Camundongos , Mutação , Defeitos do Tubo Neural/fisiopatologia , Fenótipo , Gravidez , Crânio/anormalidades , Crânio/fisiopatologia , Disrafismo Espinal/fisiopatologia , Sequenciamento Completo do Exoma
19.
J Neurosurg Pediatr ; 20(5): 464-470, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28862518

RESUMO

OBJECTIVE The aim of this study was to establish optimal electric stimulation parameters for intraoperatively monitoring the bulbocavernosus reflexes (BCRs) in infants. METHODS The authors retrospectively reviewed the medical records of all infants (age < 24 months) who had undergone an untethering operation for tethered cord syndrome between May 2013 and February 2014 at a single institution and whose baseline BCR had been elicited during surgery. Using different combinations of stimulation parameters-number of stimulation pulses: 4 or 8 pulses, interpulse interval: 1, 2, or 5 msec, and polarity of stimulation: biphasic or monophasic-the authors compared the relative mean amplitude of 10 BCR responses (rmaBCRs) to each combination of parameters. RESULTS The rmaBCRs were larger with the 8-pulse stimulations than with the 4-pulse stimulations (p < 0.0001). There was a tendency, though not statistically significant, for larger rmaBCRs to be obtained with the longer interpulse interval in the 8-pulse stimulation (p = 0.1289). The biphasic stimulation produced larger rmaBCRs than the monophasic stimulation (p = 0.0005). CONCLUSIONS Biphasic 8-pulse stimulations with 5-msec or 2-msec intervals yield the largest BCR responses. Considering that an 8-pulse stimulation with 5-msec intervals may overlap the onset of the BCR, a biphasic 8-pulse stimulation with 2-msec intervals is recommended as the optimal stimulation paradigm to monitor intraoperative BCRs in infants.


Assuntos
Estimulação Elétrica/métodos , Eletrodiagnóstico/métodos , Reflexo , Feminino , Humanos , Lactente , Masculino , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/cirurgia , Reflexo/fisiologia , Estudos Retrospectivos
20.
BMJ Case Rep ; 20172017 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-28951509

RESUMO

Neural Tube defects are one of the most common congenital disorders, presenting in a paediatric rehabilitation set-up. With its wide spectrum of clinical presentation and possible complications, the condition can significantly impact an individual's functional capacity and quality of life. The condition also affects the family of the child leaving them with a lifelong impairment to cope up with. Through this 16-year-old child, we shed light on the effects of providing rehabilitation, even at a later stage and its benefits. We also get a glimpse of difficulties in availing rehabilitation services in developing countries and the need to reach out many more neglected children like him with good functional abilities.


Assuntos
Pessoas com Deficiência/reabilitação , Incontinência Fecal/reabilitação , Saúde Holística , Defeitos do Tubo Neural/reabilitação , Modalidades de Fisioterapia , Lesão por Pressão/prevenção & controle , Incontinência Urinária/reabilitação , Sucesso Acadêmico , Adolescente , Aconselhamento Diretivo , Pessoas com Deficiência/psicologia , Incontinência Fecal/fisiopatologia , Incontinência Fecal/psicologia , Humanos , Comunicação Interdisciplinar , Masculino , Mães/educação , Defeitos do Tubo Neural/fisiopatologia , Defeitos do Tubo Neural/psicologia , Educação de Pacientes como Assunto , Qualidade de Vida , Serviços de Saúde Escolar , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/fisiopatologia , Incontinência Urinária/psicologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA