RESUMO
Integrating health interventions in a growing economy like India, with a birth cohort of 27 million/year, one-fifth of all childbirths, and approximately one-third of neonatal deaths globally, is a challenge. While mortality statistics are vital, intact survival and early preventive healthcare, such as newborn screening (NBS), are paramount. The appalling lack of information about the precise burden of metabolic errors at the state/national level or a mandated program encouraged a feasibility study of NBS in a prospective newborn cohort recruited in Delhi State (November 2014-April 2017) using a public-private partnership mode. The major determinants for effective implementation of universal NBS at the national level and limitations encountered are discussed in this report. Data to generate the 'core' panel for screening, sustained training of healthcare personnel, dissemination of the power of NBS to ensure neonatal/societal health to the public, and a 'national policy' emerge as priorities in a developing country.
RESUMO
Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported. Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018. Methods: A prospective registry at a tertiary care teaching institute. Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET. Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET.
Assuntos
Distonia , Tremor Essencial , Doença de Parkinson , Humanos , Masculino , Feminino , Tremor/diagnóstico , Tremor/epidemiologia , Tremor/etiologia , Tremor Essencial/diagnóstico , Tremor Essencial/epidemiologia , Tremor Essencial/complicações , Atenção Terciária à Saúde , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Distonia/complicações , Sistema de RegistrosRESUMO
The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are reportedly higher. Previous studies suggest that age associated transcriptional changes in lung and immune system results in a proinflammatory state and increased susceptibility to infectious lung diseases. Similarly, SARS-CoV-2 infection could augment ageing-related gene expression alterations resulting in severe outcomes in elderly patients. To identify genes that can potentially increase covid-19 disease severity in ageing people, we compared age associated gene expression changes with disease-associated expression changes in lung/BALF and whole blood obtained from publicly available data. We observed (i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group, respectively; (ii) a more pronounced overlap in blood compared to lung; and (iii) a similar overlap between host genes interacting with SARS-CoV-2 and ageing blood transcriptome. Pathway enrichment analysis of overlapping gene sets suggest that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and comorbidities. Further, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations
RESUMO
Background: Fragile X syndrome is the most common cause of inherited X-linked mental retardation. It is due to a mutation in a gene on X chromosome leading to hyper-expansion of a trinucleotide repeat sequence. The two most common Fragile sites with clinical significance are FRAXA at Xq27.3 comprising CGG repeat and a more distal FRAXE associated with amplification of a GCC repeat, located at Xq28. The frequency of occurrence of Fragile X syndrome is estimated to be 1/4000 male births. Screening of referrals for the mutations associated with the Fragile X syndrome constitutes a significant workload in many genetic laboratories. Aims: The aim of the present study was to establish the use of PCR based simple and rapid method of initial screening of samples, so that only a minority of samples tested positive with the above methods need to be screened by Southern blotting which is more time consuming and involves use of radioactive material. materials and Methods: Study includes 294 patients with mental retardation. DNA extracted from blood was used for simultaneous amplification of the triplet repeat sequences at the FRAXA and FRAXE loci. Secondly samples from females were analyzed for heterozygosity of normal FRAXA allele. For confirmation of the presence of an expanded FRAXA allele in all the male positive cases, Southern blot hybridization was carried out. PCR based assay was done to detect methylation of the CpG island upstream of the FMR-1 gene. Results: Out of the 294 cases 23 (7.8%) were found to be having full mutation (FM) for FRAXA (21 males, 1 female & 1 male with mosaic FM/PM) and 13 females as having premutation (PM). All these 36 cases were confirmed by Southern blotting using appropriate probes. Among the females the heterozygosity for FRAXA allele was found to be 46%. Conclusion: Non-radioactive PCR methods are efficient and rapid test for intial screening of samples for the presence of FRAXA and FRAXE mutations. Since a large majority of referrals do not have Fragile X, this economical and reliable method reduces the number of samples needing Southern blotting.
RESUMO
Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance which is also governed by non-genetic factors. Candidate genes identified on the basis of biochemical and pharmacological evidence are being tested for linkage and association studies. Neurotransmitters, especially dopamine and serotonin have been widely implicated in its etiology. Genome scan of all human chromosomes with closely spaced polymorphic markers is being used for linkage studies. The completion and availability of the first draft of Human Genome Sequence has provided a treasure-trove that can be utilized to gain insight into the so far inaccessible regions of the human genome. Significant technological advances for identification of single nucleo-tide polymorphisms (SNPs) and use of microarrays have further strengthened research methodologies for genetic analysis of complex traits. In this review, we summarize the evolution of schizophrenia genetics from the past to the present, current trends and future direction of research.
Assuntos
Antecipação Genética , Catecol O-Metiltransferase/genética , Cromossomos Humanos/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina , Genoma Humano , História do Século XX , Humanos , Índia , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras/genética , Biologia Molecular , Monoaminoxidase/genética , Proteínas do Tecido Nervoso , Polimorfismo de Nucleotídeo Único/genética , Receptores Dopaminérgicos/genética , Receptores de Serotonina/genética , Esquizofrenia/genética , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A number of candidate genes, a majority of them from the monoaminergic pathway in the brain, have been very popular in association studies with schizophrenia, a neuropsychiatric disorder. In this study diallelic/multiallelic polymorphisms in some dopaminergic, serotonergic and membrane-phospholipid-related genes have been evaluated in a control population recruited from North India. Association, if any, of these allelic variants with schizophrenia has been tested using a case-control approach. The case data have been taken from our published family-based association studies in schizophrenia. Of the eight genes tested in this study, association with schizophrenia was observed for only two gene polymorphisms, one in the promoter region of the serotonin 2A receptor gene and the other in the tryptophan hydroxylase gene. One new allele for the dopamine transporter gene (with eight repeats, 570-bp size), not reported in any population so far, has been identified in one individual in our sample. The data generated in this study, besides providing a normative background for various disease association studies, are a significant contribution to the population-specific genome database, a currently growing requirement.