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1.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204152

RESUMO

In nature, plants are exposed to an ever-changing environment with increasing frequencies of multiple abiotic stresses. These abiotic stresses act either in combination or sequentially, thereby driving vegetation dynamics and limiting plant growth and productivity worldwide. Plants' responses against these combined and sequential stresses clearly differ from that triggered by an individual stress. Until now, experimental studies were mainly focused on plant responses to individual stress, but have overlooked the complex stress response generated in plants against combined or sequential abiotic stresses, as well as their interaction with each other. However, recent studies have demonstrated that the combined and sequential abiotic stresses overlap with respect to the central nodes of their interacting signaling pathways, and their impact cannot be modelled by swimming in an individual extreme event. Taken together, deciphering the regulatory networks operative between various abiotic stresses in agronomically important crops will contribute towards designing strategies for the development of plants with tolerance to multiple stress combinations. This review provides a brief overview of the recent developments in the interactive effects of combined and sequentially occurring stresses on crop plants. We believe that this study may improve our understanding of the molecular and physiological mechanisms in untangling the combined stress tolerance in plants, and may also provide a promising venue for agronomists, physiologists, as well as molecular biologists.


Assuntos
Produtos Agrícolas/fisiologia , Estresse Fisiológico/fisiologia , Produtos Agrícolas/crescimento & desenvolvimento , Homeostase , Fotossíntese/fisiologia , Espécies Reativas de Oxigênio/metabolismo
2.
Plant Physiol Biochem ; 166: 593-604, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34186283

RESUMO

In rice (Oryza sativa), Si nutrition is known to improve salinity tolerance; however, limited efforts have been made to elucidate the underlying mechanism. Salt-Overly Sensitive (SOS) pathway contributes to salinity tolerance in plants in a major way which works primarily through Na+ exclusion from the cytosol. SOS1, a vital component of SOS pathway is a Na+/H+ antiporter that maintains ion homeostasis. In this study, we evaluated the effect of overexpression of Oryza sativa SOS1 (OsSOS1) in tobacco (cv. Petit Havana) and rice (cv. IR64) for modulating its response towards salinity further exploring its correlation with Si nutrition. OsSOS1 transgenic tobacco plants showed enhanced tolerance to salinity as evident by its high chlorophyll content and maintaining favorable ion homeostasis under salinity stress. Similarly, transgenic rice overexpressing OsSOS1 also showed improved salinity stress tolerance as shown by higher seed germination percentage, seedling survival and low Na+ accumulation under salinity stress. At their mature stage, compared with the non-transgenic plants, the transgenic rice plants showed better growth and maintained better photosynthetic efficiency with reduced chlorophyll loss under stress. Also, roots of transgenic rice plants showed reduced accumulation of Na+ leading to reduced oxidative damage and cell death under salinity stress which ultimately resulted in improved agronomic traits such as higher number of panicles and fertile spikelets per panicle. Si nutrition was found to improve the growth of salinity stressed OsSOS1 rice by upregulating the expression of Si transporters (Lsi1 and Lsi2) that leads to more uptake and accumulation of Si in the rice shoots. Metabolite profiling showed better stress regulatory machinery in the transgenic rice, since they maintained higher abundance of most of the osmolytes and free amino acids.


Assuntos
Oryza , Oryza/genética , Proteínas de Plantas/genética , Salinidade , Estresse Salino , Tolerância ao Sal , Silício/farmacologia , Estresse Fisiológico
3.
J Exp Bot ; 71(2): 653-668, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31626290

RESUMO

Edaphic factors such as salinity, sodicity, and drought adversely affect crop productivity, either alone or in combination. Despite soil sodicity being reported as an increasing problem worldwide, limited efforts have been made to address this issue. In the present study, we aimed to generate rice with tolerance to sodicity in conjunction with tolerance to salinity and drought. Using a fusion gene from E. coli coding for trehalose-6-phosphate synthase/phosphatase (TPSP) under the control of an ABA-inducible promoter, we generated marker-free, high-yielding transgenic rice (in the IR64 background) that can tolerate high pH (~9.9), high EC (~10.0 dS m-1), and severe drought (30-35% soil moisture content). The transgenic plants retained higher relative water content (RWC), chlorophyll content, K+/Na+ ratio, stomatal conductance, and photosynthetic efficiency compared to the wild-type under these stresses. Positive correlations between trehalose overproduction and high-yield parameters were observed under drought, saline, and sodic conditions. Metabolic profiling using GC-MS indicated that overproduction of trehalose in leaves differently modulated other metabolic switches, leading to significant changes in the levels of sugars, amino acids, and organic acids in transgenic plants under control and stress conditions. Our findings reveal a novel potential technological solution to tackle multiple stresses under changing climatic conditions.


Assuntos
Secas , Oryza/fisiologia , Salinidade , Solo/química , Trealose/biossíntese , Concentração de Íons de Hidrogênio , Oryza/genética , Oryza/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/fisiologia
4.
Sci Rep ; 9(1): 11015, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31337776

RESUMO

 A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

5.
Sci Rep ; 8(1): 7621, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29752473

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

6.
Sci Rep ; 8(1): 4072, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29511223

RESUMO

Cytoskeleton plays a vital role in stress tolerance; however, involvement of intermediate filaments (IFs) in such a response remains elusive in crop plants. This study provides clear evidence about the unique involvement of IFs in cellular protection against abiotic stress in rice. Transcript abundance of Oryza sativa intermediate filament (OsIF) encoding gene showed 2-10 fold up-regulation under different abiotic stress. Overexpression of OsIF in transgenic rice enhanced tolerance to salinity and heat stress, while its knock-down (KD) rendered plants more sensitive thereby indicating the role of IFs in promoting survival under stress. Seeds of OsIF overexpression rice germinated normally in the presence of high salt, showed better growth, maintained chloroplast ultrastructure and favourable K+/Na+ ratio than the wild type (WT) and KD plants. Analysis of photosynthesis and chlorophyll a fluorescence data suggested better performance of both photosystem I and II in the OsIF overexpression rice under salinity stress as compared to the WT and KD. Under salinity and high temperature stress, OsIF overexpressing plants could maintain significantly high yield, while the WT and KD plants could not. Further, metabolite profiling revealed a 2-4 fold higher accumulation of proline and trehalose in OsIF overexpressing rice than WT, under salinity stress.


Assuntos
Resposta ao Choque Térmico , Filamentos Intermediários/metabolismo , Oryza/fisiologia , Fotossíntese , Salinidade , Estresse Fisiológico , Expressão Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Filamentos Intermediários/genética , Metabolômica , Oryza/efeitos dos fármacos , Oryza/genética , Oryza/efeitos da radiação , Prolina/análise , RNA Mensageiro/análise , Trealose/análise
7.
Curr Med Res Opin ; 34(5): 911-921, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29278015

RESUMO

PURPOSE: Cancer remains a significant cause of morbidity and mortality across the globe. A recent report suggests around 14.1 million new cases and 8.2 million cancer-related deaths, which are expected to reach 21.7 million and 13 million by 2030 worldwide, respectively. MATERIALS AND METHODS: Because of highly complex mechanisms of cancer progression, it is important to explore and develop new innovative technologies which are more efficient compared with presently available treatment options. RESULTS: Currently, chemotherapy, radiation and surgery are the most commonly used cancer treatment methods. In the last decade, nanomedicine emerged as an alternative treatment option that uses specific drug-delivery systems, improves efficacy of drugs and reduces detrimental side effects to normal tissues. CONCLUSION: In this review, we have summarized cancer nanomedicines (active and passive drug delivery) available in the market. We have also discussed other nanomedicines that are at different stages of clinical trials.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Humanos , Nanomedicina
8.
Plant Cell Environ ; 41(5): 1186-1200, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28425127

RESUMO

Crop plants face a multitude of diverse abiotic and biotic stresses in the farmers' fields. Although there now exists a considerable knowledge of the underlying mechanisms of response to individual stresses, the crosstalk between response pathways to various abiotic and biotic stresses remains enigmatic. Here, we investigated if the cytotoxic metabolite methylglyoxal (MG), excess of which is generated as a common consequence of many abiotic and biotic stresses, may serve as a key molecule linking responses to diverse stresses. For this, we generated transgenic rice plants overexpressing the entire two-step glyoxalase pathway for MG detoxification. Through assessment of various morphological, physiological and agronomic parameters, we found that glyoxalase-overexpression imparts tolerance towards abiotic stresses like salinity, drought and heat and also provides resistance towards damage caused by the sheath blight fungus (Rhizoctonia solani) toxin phenylacetic acid. We show that the mechanism of observed tolerance of the glyoxalase-overexpressing plants towards these diverse abiotic and biotic stresses involves improved MG detoxification and reduced oxidative damage leading to better protection of chloroplast and mitochondrial ultrastructure and maintained photosynthetic efficiency under stress conditions. Together, our findings indicate that MG may serve as a key link between abiotic and biotic stress response in plants.


Assuntos
Lactoilglutationa Liase/metabolismo , Oryza/fisiologia , Aldeído Pirúvico/metabolismo , Tioléster Hidrolases/metabolismo , Antioxidantes/metabolismo , Brassica/enzimologia , Brassica/genética , Morte Celular , Cloroplastos/ultraestrutura , Secas , Expressão Gênica , Temperatura Alta , Lactoilglutationa Liase/genética , Mitocôndrias/ultraestrutura , Oryza/enzimologia , Oryza/genética , Oryza/ultraestrutura , Fenilacetatos/toxicidade , Fotossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Aldeído Pirúvico/análise , Salinidade , Estresse Fisiológico , Tioléster Hidrolases/genética
9.
Plant Cell Environ ; 41(5): 947-969, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28337760

RESUMO

High salinity is one of the major problems in crop productivity, affecting seed germination as well as yield. In order to enhance tolerance of crops towards salinity, it is essential to understand the underlying physiological and molecular mechanisms. In this endeavor, study of contrasting genotypes of the same species differing in their response towards salinity stress can be very useful. In the present study, we have investigated temporal differences in morphological, physiological and proteome profiles of two contrasting genotypes of rice to understand the basis of salt tolerance. When compared to IR64 rice, Pokkali, the salt-tolerant wild genotype, has enhanced capacity to cope with stress, better growth rate and possesses efficient antioxidant system, as well as better photosynthetic machinery. Our proteome studies revealed a higher and an early abundance of proteins involved in stress tolerance and photosynthesis in Pokkali in comparison with IR64, which, in contrast, showed greater changes in metabolic machinery even during early duration of stress. Our findings suggest important differences in physicochemical and proteome profiles of the two genotypes, which may be the basis of observed stress tolerance in the salt-tolerant Pokkali.


Assuntos
Oryza/fisiologia , Proteoma , Tolerância ao Sal , Antioxidantes/metabolismo , Produtos Agrícolas , Meio Ambiente , Oryza/genética , Oryza/crescimento & desenvolvimento , Fotossíntese/fisiologia , Proteômica , Salinidade , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia
10.
Electron Physician ; 9(9): 5304-5309, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29038714

RESUMO

BACKGROUND: Changes in the anatomical structures and function of the ear can result in ear diseases, and may affect all age groups including the elderly as a result of aging. OBJECTIVE: To identify the frequency and types of ear diseases among the elderly attending Abdullah bin Abdul-Aziz bin Musa'ed Al Saud hospital, Arar city, in the Northern Province of KSA, and factors associated with ear infections among them. METHODS: This cross-sectional hospital based study conducted from December 2016 through May 2017 included 138 elderly participants. A questionnaire was designed for collecting data about socio-demographic variables, the frequency and types of ear diseases among participants, and factors associated with ear infections among them. Data were analyzed by SPSS version 15, using descriptive statistics and Chi-Square test. RESULTS: Findings showed that 49.3% of the participants were suffering from ear disease. Hearing impairment was detected in 37% of the elderly people studied. In addition, 9.4% and 2.9 % of the participants suffered from otitis media and otitis interna, respectively. None of the studied factors had a significant effect on the development and pattern of ear infection among the studied population. CONCLUSION: Ear diseases were found among the participants with variable rates. More than one third of respondents suffered from hearing impairment. Ear infections were detected in lower rates. Although these problems are not life threating, they negatively impact the quality of life, and measures are needed for prevention and control.

11.
Methods Mol Biol ; 1679: 83-95, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28913795

RESUMO

Salinity and drought are interconnected, causing phenotypic, physiological, biochemical, and molecular changes in a cell. These stresses are the major factors adversely affecting growth and productivity in cereals. Genetic engineering methods have advanced to enable development of genotypes with improved salinity and drought tolerance. The resulting transgenic plant produces a group of progenies which includes moderate to high-stress tolerant transgenic lines. Development of reproducible screening methods to identify high-stress tolerant germplasm under laboratory, greenhouse, or field conditions is must. Further, field level demonstration of improved phenotypes and yield under salinity and drought stress conditions is both challenging and expensive. Fast and efficient screening techniques that could be used to screen transgenic lines under greenhouse conditions, for salt and drought stress tolerance, may contribute toward the identification of promising lines for field conditions. This chapter provides information on various approaches which can be developed during different stages of plant development for selecting salinity and drought tolerant plants in cereals, especially wheat.


Assuntos
Aclimatação/genética , Secas , Plantas Geneticamente Modificadas , Salinidade , Tolerância ao Sal/genética , Triticum/genética , Triticum/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação/genética , Ensaios de Triagem em Larga Escala , Fenótipo , Fotossíntese/genética , Espécies Reativas de Oxigênio , Reprodução/genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Estresse Fisiológico/genética , Triticum/crescimento & desenvolvimento
12.
Sci Rep ; 7(1): 11904, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28928401

RESUMO

Saffron is one of the most expensive spices of the world. Since this spice is triploid and meiosis is unusual, it cannot reproduce sexually like other plants; rather, it is propagated vegetatively via an underground corm, which can withstand a long dry dormant period before sprouting. Thus, corms are indispensable to saffron propagation. To identify and analyse signature metabolites associated with the 'dormancy-sprouting' process, non-targeted GC-MS was performed at different stages of corm development. Comparative metabolite profiling reflected dissimilar profiles among the stages as portrayed by differential cluster patterns of metabolites in the PCA and PLS-DA analysis. Correlation analysis revealed the interdependencies of individual metabolites and metabolic pathway. At the onset of stage 2, characterized by the initiation and differentiation of leaf primordia, a shift from dormancy to active metabolism occurred as derived from the increased abundance of sugars and other metabolites involved in the tricarboxylic acid cycle, glycolytic, amino acid and fatty acid pathways. These changes contribute to sprouting and vegetative growth of the corm. The present study provides new insights into saffron corm composition and metabolite changes associated with various stages of corm development and may pave the way for achieving agronomical improvements in this economically important spice.


Assuntos
Aminoácidos/metabolismo , Crocus/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Açúcares/metabolismo , Crocus/metabolismo , Redes e Vias Metabólicas , Metaboloma , Plântula/metabolismo
13.
Food Chem ; 212: 663-70, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27374582

RESUMO

Heating/frying and reuse of edible fats/oils induces chemical changes such as formation of trans fatty acids (TFAs). The aim of this study was to investigate the effect of heating/frying on formation of TFAs in fats/oils. Using gas chromatography with flame ionisation detector, TFA was estimated in six commonly used fat/oils in India (refined soybean oil, groundnut oil, olive oil, rapeseed oil, clarified butter, partially hydrogenated vegetable oil), before and after subjecting them to heating/frying at 180°C and 220°C. All six fats/oils subjected to heating/frying demonstrated an increase in TFAs (p<0.001), saturated fatty acids (p<0.001) and decrease in cis-unsaturated fatty acids (p<0.001). The absolute increase in TFA content of edible oils (after subjecting to heating/reheating) ranged between 2.30±0.89g/100g and 4.5±1.43g/100g; amongst edible fats it ranged between 2.60±0.38g/100g and 5.96±1.94g/100g. There were no significant differences between the two treatment groups (heating and frying; p=0.892). Considering the undesirable health effects of TFA, appropriate guidelines for heating/re-frying of edible fats/oils by Asian Indians should be devised.


Assuntos
Culinária , Óleos Vegetais/química , Ácidos Graxos trans/análise , Manteiga/análise , Cromatografia Gasosa , Gorduras na Dieta/análise , Ésteres/química , Ionização de Chama , Temperatura Alta , Índia , Óleo de Amendoim , Óleo de Soja/análise
14.
J Plant Physiol ; 176: 36-46, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25543954

RESUMO

Plants have evolved a number of molecular strategies and regulatory mechanisms to cope with abiotic stresses. Among the various key factors/regulators, transcription factors (TFs) play critical role(s) towards regulating the gene expression patterns in response to stress conditions. Altering the expression of the key TFs can greatly influence plant stress tolerance. OsHBP1b (accession no. KM096571) is one such TF belonging to bZIP family, localized within the Saltol QTL, whose expression is induced upon salinity treatment in the rice seedlings. qRT-PCR based expression studies for OsHBP1b in seedlings of contrasting genotypes of rice showed its differential regulation in response to salinity stress. A GFP based in vivo study showed that the OsHBP1b protein is nuclear localized and possesses the trans-activation activity. As compared to the WT tobacco plants, the transgenic plants ectopically expressing OsHBP1b showed better survival and favourable osmotic parameters (such as germination and survival rate, membrane stability, K(+)/Na(+) ratio, lipid peroxidation, electrolyte leakage and proline contents) under salinity and drought stress. Under salinity conditions, the transgenic plants accumulated lower levels of reactive oxygen species as compared to the WT. It was also accompanied by higher activities of antioxidant enzymes (such as ascorbate peroxidase and superoxide dismutase), thereby demonstrating that transgenic plants are physiologically better adapted towards the oxidative damage. Taken together, our findings suggest that OsHBP1b contributes to abiotic stress tolerance through multiple physiological pathways and thus, may serve as a useful 'candidate gene' for improving multiple stress tolerance in crop plants.


Assuntos
Antioxidantes/metabolismo , Núcleo Celular/metabolismo , Clorofila/metabolismo , Secas , Histonas/metabolismo , Proteínas de Plantas/metabolismo , Salinidade , Estresse Fisiológico , Adaptação Fisiológica/genética , Sequência de Aminoácidos , Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genótipo , Germinação , Dados de Sequência Molecular , Oryza , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio/metabolismo , Plântula/genética , Estresse Fisiológico/genética , Tabaco/genética , Técnicas do Sistema de Duplo-Híbrido
15.
NeuroRehabilitation ; 24(4): 333-40, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19597271

RESUMO

OBJECTIVE: To assess the validity and reliability of a Numeric Rating Scale (NRS) for the measurement of spasticity in multiple sclerosis. DESIGN: Longitudinal study with multiple comparators over two clinic visits. SETTING: Rehabilitation Centre in the North East of England, UK. SUBJECTS: A total of thirty-five patients, with a diagnosis of multiple sclerosis (MS) that were attending a rehabilitation clinic. RESULTS: The test/re-test reliability of the NRS showed there was a high correlation between the two visits (r = 0.672). Construct validity was assessed by examining the relationship between the mean spasticity NRS and each of the other spasticity assessment tools. There was a statistically significant correlation between subject's mean NRS diary scores and the Modified Ashworth Scale scores at both visits (Visit 1, r = 0.459, p = 0.0056; Visit 2, r = 0.446, p = 0.0106). There was a moderate, statistically significant correlation between the mean NRS diary scores and the Tardieu Scale (Visit 1, r = 0.429, p = 0.0113; Visit 2, r = 0.407, p = 0.0209). CONCLUSIONS: The spasticity NRS has been shown to be a valid and reliable tool in the assessment of spasticity with a moderate to high level of correlation with other clinician rated instruments used to assess spasticity.


Assuntos
Avaliação da Deficiência , Esclerose Múltipla/complicações , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/etiologia , Índice de Gravidade de Doença , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/reabilitação , Espasticidade Muscular/reabilitação , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Valores de Referência , Reprodutibilidade dos Testes
16.
J Hum Genet ; 51(9): 827-831, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16897189

RESUMO

Cone-rod retinal dystrophy (CORD) characteristically leads to early impairment of vision due to the simultaneous involvement of both cone and rod photoreceptor cells. Several loci/genes have been identified for CORD, including the cone-rod dystrophy (CORD8) locus [OMIM#605549] identified for a Pakistani family. All members of this family underwent detailed clinical re-examination to determine the nature of the dystrophy. All affected individuals suffered from bilateral CORD8 with an autosomal recessive mode of inheritance. The CORD8 locus, mapped on chromosome 1q12-q24, consisted of a very large critical disease region of 21 cM. Analysis with more recently available microsatellite markers within the reported region showed heterozygosity with some of the new markers, and the crossovers lead to a refinement of the disease region from 21 to 11.53 cM. Mutation screening has excluded some of the candidate genes in the region. The disease phenotype of this family could be due to a mutation in a novel gene located within the refined CORD8 locus.


Assuntos
Retinite Pigmentosa/genética , Adulto , Cromossomos Humanos Par 1/genética , Consanguinidade , Feminino , Genes Recessivos , Ligação Genética , Humanos , Masculino , Paquistão , Linhagem , Retinite Pigmentosa/patologia
18.
Arch Ophthalmol ; 122(7): 1029-37, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15249368

RESUMO

OBJECTIVES: To describe the phenotype of Leber congenital amaurosis (LCA) in 26 probands with mutations in aryl hydrocarbon receptor interacting protein-like 1 protein (AIPL1) and compare it with phenotypes of other LCA-related genes. To describe the electroretinogram (ERG) in heterozygote carriers. METHODS: Patients with AIPL1-related LCA were identified in a cohort of 303 patients with LCA by polymerase chain reaction single-strand confirmational polymorphism mutation screening and/or direct sequencing. Phenotypic characterization included clinical and ERG evaluation. Seven heterozygous carrier parents also underwent ERG testing. RESULTS: Seventeen homozygotes and 9 compound heterozygotes were identified. The W278X mutation was most frequent (48% of alleles). Visual acuities ranged from light perception to 20/400. Variable retinal appearances, ranging from near normal to varying degrees of chorioretinal atrophy and intraretinal pigment migration, were noted. Atrophic and/or pigmentary macular changes were present in 16 (80%) of 20 probands. Keratoconus and cataracts were identified in 5 (26%) of 19 patients, all of whom were homozygotes. The ERG of a parent heterozygote carrier revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. CONCLUSIONS: The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset. Rod ERG abnormalities may be present in heterozygous carriers of AIPL1 mutations. CLINICAL RELEVANCE: Understanding and recognizing the phenotype of LCA may help in defining the course and severity of the disease. Identifying the gene defect is the first step in preparation for therapy since molecular diagnosis in LCA will mandate the choice of treatment.


Assuntos
Cegueira/genética , Proteínas de Transporte/genética , Mutação , Fenótipo , Degeneração Retiniana/genética , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Alelos , Cegueira/congênito , Cegueira/patologia , Catarata/congênito , Catarata/genética , Catarata/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Eletrorretinografia , Proteínas do Olho , Humanos , Lactente , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Degeneração Retiniana/congênito , Degeneração Retiniana/patologia , Acuidade Visual
19.
Exp Eye Res ; 76(3): 343-8, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12573663

RESUMO

To map the disease loci several Pakistani families suffering from autosomal recessive retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium and Leber congenital amaurosis (LCA) were analyzed. Analysis revealed close genetic linkage between the disease phenotype of some of the families (3330RP, 111RP and 010LCA) and the microsatellite markers on chromosome 1q31. Mutation screening of the candidate gene CRB1 revealed a G to A transversion in exon 7 in arRP family 330RP and a T to C substitution in another arRP family, 111RP. In exon 9 of the CRB1 gene a T to C transversion was found in the family suffering from LCA (010LCA). The LCA phenotype of another family (011LCA) in which the CRB1 locus was excluded, showed linkage with microsatellite markers D17S1294 and D17S796 on chromosome 17p13.1. The association of the candidate gene GUCY2D (17p13.1) with the disease phenotype was excluded as no disease-associated mutation was found in any of its exons. Mutation screening of another candidate gene, AIPL1 located in the same region, showed a novel homozygous C to A substitution in exon 2. These sequence changes are unique for the Pakistani families and some of these have not been reported previously.


Assuntos
Mutação , Atrofia Óptica Hereditária de Leber/genética , Retinite Pigmentosa/genética , Adolescente , Adulto , Criança , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 17/genética , Análise Mutacional de DNA , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Linhagem
20.
Invest Ophthalmol Vis Sci ; 43(7): 2083-7, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12091400

RESUMO

PURPOSE: To map the disease locus in a four-generation, consanguineous Pakistani family affected by autosomal dominant congenital nuclear cataract (adNCat). All affected individuals had early onset of bilateral nuclear cataract. METHODS: Genomic DNA from family members was typed for alleles at more than 300 known polymorphic genetic markers by polymerase chain reaction. The lod scores were calculated by using two-point linkage analysis of the genotyping data. RESULTS: The maximum lod score, 4.05, was obtained for the marker D2S2333. Proximal and distal crossovers were observed with markers D2S286 and D2S1790, respectively. These crossovers define the critical disease locus to an interval of approximately 9 centimorgans (cM). CONCLUSIONS: Linkage analysis identified a novel locus for adNCat on chromosome 2p12 in a Pakistani family. A genome database analysis of the target interval is being undertaken to identify candidate gene(s) for the disease.


Assuntos
Catarata/genética , Cromossomos Humanos Par 2/genética , Genes Dominantes , Núcleo do Cristalino/patologia , Adulto , Idoso , Catarata/congênito , Catarata/patologia , Mapeamento Cromossômico , Consanguinidade , DNA/análise , Análise Mutacional de DNA , Feminino , Ligação Genética , Genótipo , Humanos , Escore Lod , Masculino , Paquistão , Linhagem , Reação em Cadeia da Polimerase
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