Pharmacogenetics Reality Or Fction? Or Are We There Yet?

[No abstract available]6902:00:00151152Twardowschy, C.A., Werneck, L.C., Scola, R.H., Depaola, L., Silvado, C.E., CYP2C9 polymorphisms in patients with epilepsy. Genotypic frequency analyzes and phe-nytoin adverse reactions correlations (2011) Arq Neurop-siquiatr, 69, pp. 153-158Glauser, T., Bem-Menachen, E., Bourgeois, B., ILAE treatment guidelines: Evidence-based analysis of an-tiepileptic drug efcacy and efectiveness as initialmonotherapy for epileptic seizures and syndromes (2006) Epilepsia, 47, pp. 1094-1120Gidal, B.E., French, J.A., Grossman, P., le Teuf, G., Assessment of potential drug interactions in patients with epilepsy:Impact of age and sex (2009) Neurology, 72, pp. 419-425Vogel, F., Moderne probleme der humangenetik (1959) Ergeb Inn Med Kinder-heilkd, 12, pp. 52-125Johnson, J.A., Pharmacogenetics: Potential for individualized drug therapy through genetics (2003) Trends Genet, 19, pp. 660-666Initial sequencing and analysis of the human genome (2001) Nature, 409, pp. 860-921. , International Human Genome Sequence ConsortiumJordan, D.M., Ramensky, V.E., Sunyaev, S.R., Human allelic variation: Perspective from protein function, structure, and evolution (2010) Curr Opin Struct Biol, 20, pp. 342-350Evans, B.J., Establishing clinical utility of pharmacogenetic tests in the post-FDAAA era (2010) Clin Pharmacol Ther, 88, pp. 749-751Hamburg, M.A., Collins, F.S., The path to personalized medicine (2010) N Engl J Med, 363, pp. 301-304(2009) Carbamazepine (market As Car-batrol, Equetro, Tegretol and Generics), , http:www.fda.gov/cder/drug/InfoSheet/HCP/carba-mazepineHCP.htm, Information for healthcare professionals, FDA Alert 12/12/07, updated 1/31/0

Do We Need A New Look In The Definition Of X-linked Recessive Disorders? [precisamos Ter Uma Nova Visão Da Definição Das Desordens Recessivas Ligadas Ao X?]

[No abstract available]707483484Rosenberg, R.N., Translational research in neurology and neuroscience 2010-2011 (2010) Arch Neurol, 67, p. 1176Uchihara, T., Expanding morphological dimensions in neuropathology, from sequence biology to pathological sequences and clinical consequences (2011) Neuropathol, 31, pp. 201-207Berciano, J., Peripheral neuropathies: Molecular diagnosis of Charcot-Marie-Tooth disease (2011) Nat Rev Neurol, 7, pp. 305-306Tabatabai, G., Hegi, M., Stupp, R., Weller, M., Clinical implications of molecular neuropathology and biomarkers for malignant glioma (2012) Curr Neurol Neurosci Rep, 12, pp. 302-307Dobyns, W.B., Filauro, A., Tomson, B.N., Inheritance of most X-linked traits is not dominant or recessive, just X-linked (2004) Am J Med Genet, 129, pp. 136-143Benson, K.R., Morgan's resistance to the chromosome theory (2001) Nat Rev Genet, 2, pp. 469-474Morgan, T.H., Sturtevant, A.H., Muller, H.J., Bridges, C.B., (1922) The Mechanism of Mendelian Heredity, , New York: Henry Holt & CompanyLourenço, C.M., Simão, G.N., Santos, A.C., Marques, W., X-Linked adrenoleukodystrophy in heterozygous female patients: Women are not just carriers (2012) Arq Neuropsiquiatr, 70, pp. 487-491Powers, J.M., Moser, H.W., Moser, A.B., Ma, C.K., Elias, S.B., Norum, R.A., Pathologic findings in adrenoleukodystrophy heterozygotes (1987) Arch Pathol Lab Med, 111, pp. 151-153Nussbaum, R.L., McInnes, R.R., Willard, H.F., Boerkoel, C.F.R., (2007) Thompson & Thompson: Genetics In Medicine, , Philadelphia: W.B. Saunders CoLyon, M.F., Sex chromatin and gene action in the mammalian X chromosome (1962) Am J Hum Genet, 14, pp. 135-148Willard, H.F., The sex chromosomes and X chromosome inactivation (2000) The Metabolic and Molecular Bases of Inherited Diseases, pp. 1191-1221. , In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, 8th edition. New York: McGraw-HillOrstavik, K.H., X chromosome inactivation in clinical practice (2009) Hum Genet, 126, pp. 363-37

Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.1129113

Role of non-coding RNAs in non-aging-related neurological disorders

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOProtein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regula518CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãosem informação2016/22447-52011/506802013/07559-

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.72272

Rqc: a bioconductor package for quality control of high-throughput sequencing data

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOAs sequencing costs drop with the constant improvements in the field, next-generation sequencing becomes one of the most used technologies in biological research. Sequencing technology allows the detailed characterization of events at the molecular level,87CN2114FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2013/24801-2sem informaçã

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxi4912FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2007/57559-9; 2013/07559-3sem informaçã

Methodological differences can affect sequencing depth with a possible impact on the accuracy of genetic diagnosis

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFINANCIADORA DE ESTUDOS E PROJETOS - FINEPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFor a better interpretation of variants, evidence-based databases, such as ClinVar, compile data on the presumed relationships between variants and phenotypes. In this study, we aimed to analyze the pattern of sequencing depth in variants from whole-exome43216FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFINANCIADORA DE ESTUDOS E PROJETOS - FINEPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFINANCIADORA DE ESTUDOS E PROJETOS - FINEPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ2013/07559-3proj595001309494/2014-1403299/2016-0The authors thank Prof. Vera Solferini, Prof. Plinio Barbosa, Ph.D. Ticiana Mira, and Dr. Joana Prota for their contributions on technical assistance and critical review of the manuscript. This work was supported by Fundação de Amparo à Pesquisa do Estad

Molecular Diagnosis Of Huntington Disease In Brazilian Patients.

Huntington disease (HD) is a progressive neurodegenerative disorder with autosomal dominant inheritance, characterized by choreiform movements and cognitive impairment. Onset of symptoms is around 40 years of age and progression to death occurs in approximately 10 to 15 years from the time of disease onset. HD is associated with an unstable CAG repeat expansion at the 5' and of the IT15 gene. We have genotyped the CAG repeat in the IT15 gene in 44 Brazilian individuals (42 patients and 2 unaffected family members) belonging to 34 unrelated families thought to segregate HD. We found one expanded CAG allele in 32 individuals (76%) belonging to 25 unrelated families. In these HD patients, expanded alleles varied from 43 to 73 CAG units and normal alleles varied from 18 to 26 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r=0.6; p=0.0001); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2=0.4). In addition, we genotyped 25 unrelated control individuals (total of 50 alleles) and found normal CAG repeats varying from 16 to 33 units. The percentage of heterozigocity of the normal allele in the control population was 88%. In conclusion, our results showed that not all patients with the HD phenotype carried the expansion at the IT15 gene. Furthermore, molecular diagnosis was possible in all individuals, since no alleles of intermediate size were found. Therefore, molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling.5811-

A prediction algorithm for drug response in patients with mesial temporal lobe epilepsy based on clinical and genetic information

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide121FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/07559-