Pub Date : 2016-11-30DOI: 10.4172/2157-7412.C1.010
X. Paoli
{"title":"An online survey of neurologists about Charcot-Marie-Tooth disease type 1A","authors":"X. Paoli","doi":"10.4172/2157-7412.C1.010","DOIUrl":"https://doi.org/10.4172/2157-7412.C1.010","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76599667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-11-14DOI: 10.4172/2157-7412.1000311
Michelle E McClements, Peter Charbel Issa, Véronique Blouin, Robert E MacLaren
Objective: Dual vector AAV systems are being utilised to enable gene therapy for disorders in which the disease gene is too large to fit into a single capsid. Fragmented adeno-associated viral (fAAV) vectors containing single inverted terminal repeat truncated transgenes have been considered as one such gene replacement strategy. Here we aim to add to the current understanding of the molecular mechanisms employed by fAAV dual vector systems.
Methods: Oversized (>8kb) transgene constructs containing ABCA4 coding sequence were packaged as truncated fragments <5kb in size into various AAV serotypes. In vitro transductions with these fAAV vector preparations were conducted with mRNA and protein expression products assessed by way of RT-PCR, qPCR and western blot techniques.
Results: Transductions with fAAV vector preparations yielded ABCA4 mRNA, but did not generate detectable levels of protein. Sequencing of the transcript population revealed the presence of full length ABCA4 CDS with additional hybrid ABCA4 variants, indicating truncated transgenes without regions of overlap were joining and forming stable hybrid transgenes. In contrast, an ABCA4 overlapping dual vector system (OV) with a defined complementary region generated only full length mRNA transcripts plus detectable ABCA4 protein.
Conclusion: Despite previous success shown with the fAAV approach, the lack of repeatability and identification of stable hybrid transcripts capable of protein production suggests there is more refinement required before considering this approach in a clinical setting.
{"title":"A fragmented adeno-associated viral dual vector strategy for treatment of diseases caused by mutations in large genes leads to expression of hybrid transcripts.","authors":"Michelle E McClements, Peter Charbel Issa, Véronique Blouin, Robert E MacLaren","doi":"10.4172/2157-7412.1000311","DOIUrl":"https://doi.org/10.4172/2157-7412.1000311","url":null,"abstract":"<p><strong>Objective: </strong>Dual vector AAV systems are being utilised to enable gene therapy for disorders in which the disease gene is too large to fit into a single capsid. Fragmented adeno-associated viral (fAAV) vectors containing single inverted terminal repeat truncated transgenes have been considered as one such gene replacement strategy. Here we aim to add to the current understanding of the molecular mechanisms employed by fAAV dual vector systems.</p><p><strong>Methods: </strong>Oversized (>8kb) transgene constructs containing <i>ABCA4</i> coding sequence were packaged as truncated fragments <5kb in size into various AAV serotypes. <i>In vitro</i> transductions with these fAAV vector preparations were conducted with mRNA and protein expression products assessed by way of RT-PCR, qPCR and western blot techniques.</p><p><strong>Results: </strong>Transductions with fAAV vector preparations yielded <i>ABCA4</i> mRNA, but did not generate detectable levels of protein. Sequencing of the transcript population revealed the presence of full length <i>ABCA4</i> CDS with additional hybrid <i>ABCA4</i> variants, indicating truncated transgenes without regions of overlap were joining and forming stable hybrid transgenes. In contrast, an <i>ABCA4</i> overlapping dual vector system (OV) with a defined complementary region generated only full length mRNA transcripts plus detectable ABCA4 protein.</p><p><strong>Conclusion: </strong>Despite previous success shown with the fAAV approach, the lack of repeatability and identification of stable hybrid transcripts capable of protein production suggests there is more refinement required before considering this approach in a clinical setting.</p>","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"7 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2157-7412.1000311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34765863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-10-30DOI: 10.4172/2157-7412.1000312
I. Gómez-Manjón, A. Moreno-Izquierdo, M. Moreno-García, A. Delmiro, F. J. Fernández-Martínez
Introduction Hereditary heart diseases are a set of major prevalence diseases that are associated with risk of sudden death. These diseases affect with high frequency young individuals and whose genetic basis has been known in recent years. More than 100 genes are involved in these diseases. The emergence of next-generation sequencing is enabling a greater understanding of the genes involved, despite this, in a significant number of patients it is not detected the associated genetic defect. Methods In this study it was analyzed the utility of exome sequencing in a familial trio as a diagnostic tool. It was realized a retrospective study of a hypertrophic miocardiopathy case with identified genetic cause. The data generated in the sequencing study was analyzed by three bioinformatics tools: ANNOVAR (Wang K et al), Ion ReporterTM Software (Thermo Fisher. USA) and QIAGEN’s Ingenuity® Variant Analysis™ software (QIAGEN. Redwood City). Results Due to exome study, in the index case, two possibly pathogenic variants were detected: c1292G>A, in KCND3 gene and c.67087C>T, in TTN gene. Additionally, 5 probably not pathogenic variants were identified. Conclusion Exome’s next-generation sequencing is a more useful tool than Sanger or panel sequencing, due to the flexibility of it. It allows analyze interest region associated with pathology and also discover new variants and their association with diseases.
遗传性心脏病是一组与猝死风险相关的主要流行疾病。这些疾病影响年轻人的频率很高，其遗传基础近年来已为人所知。超过100个基因与这些疾病有关。新一代测序技术的出现使人们能够更好地了解相关基因，尽管如此，在相当多的患者中，并没有检测到相关的遗传缺陷。方法在本研究中，分析了外显子组测序在一个家族三人组中作为诊断工具的效用。这是实现了一项回顾性研究肥厚性心肌病病例与确定的遗传原因。测序研究中产生的数据通过三种生物信息学工具进行分析:ANNOVAR (Wang K et al)， Ion ReporterTM Software (Thermo Fisher)。美国)和QIAGEN的Ingenuity®Variant Analysis™软件(QIAGEN;雷德伍德城)。结果通过外显子组研究，在指标病例中检测到两个可能致病的变异:KCND3基因c1292G>A, TTN基因c.67087C>T。此外，鉴定出5种可能不是致病性的变异。结论Exome新一代测序技术比Sanger或panel测序更具有灵活性，是一种更实用的工具。它可以分析与病理相关的兴趣区域，也可以发现新的变异及其与疾病的关联。
{"title":"Utility of Exome Sequencing in A Familial Trio as A Diagnostic Tool in Cardiomyopathies","authors":"I. Gómez-Manjón, A. Moreno-Izquierdo, M. Moreno-García, A. Delmiro, F. J. Fernández-Martínez","doi":"10.4172/2157-7412.1000312","DOIUrl":"https://doi.org/10.4172/2157-7412.1000312","url":null,"abstract":"Introduction Hereditary heart diseases are a set of major prevalence diseases that are associated with risk of sudden death. These diseases affect with high frequency young individuals and whose genetic basis has been known in recent years. More than 100 genes are involved in these diseases. The emergence of next-generation sequencing is enabling a greater understanding of the genes involved, despite this, in a significant number of patients it is not detected the associated genetic defect. Methods In this study it was analyzed the utility of exome sequencing in a familial trio as a diagnostic tool. It was realized a retrospective study of a hypertrophic miocardiopathy case with identified genetic cause. The data generated in the sequencing study was analyzed by three bioinformatics tools: ANNOVAR (Wang K et al), Ion ReporterTM Software (Thermo Fisher. USA) and QIAGEN’s Ingenuity® Variant Analysis™ software (QIAGEN. Redwood City). Results Due to exome study, in the index case, two possibly pathogenic variants were detected: c1292G>A, in KCND3 gene and c.67087C>T, in TTN gene. Additionally, 5 probably not pathogenic variants were identified. Conclusion Exome’s next-generation sequencing is a more useful tool than Sanger or panel sequencing, due to the flexibility of it. It allows analyze interest region associated with pathology and also discover new variants and their association with diseases.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"43 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80222906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-10-28DOI: 10.4172/2157-7412.1000310
K. Skalická, L. Kovács
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease which affects nearly 12 million people in the world. Despite the intensive development of new treatment options, hemodialysis and renal replacement therapy remain the only effective treatment of the end-stage disease. However, recently there has been a significant progress in understanding the molecular pathogenesis of the disease, including the discovery of the role of the primary cilium. Recent studies have unequivocally confirmed that the change in the length of the primary cilium is an important trigger of pathological processes that results in the development and progression of ADPKD. The resumption of the primary cilium length by pharmacological regulation can stop cystic growth, prevent fibrosis, and improve kidney function. These results have opened a new era in the development of targeted drugs, so-called ciliotherapy. Early pre-clinical testing of new potential agents has brought promising results. However, there are many challenges in drug development and design of clinical trials in ADPKD, which must be overcome. This review summarized the state of knowledge about the key aspects of the primary cilium in pathogenesis of ADPKD and introduces the latest information on novel compounds that have a great potential in suppressing the development and progression of the disease.
{"title":"CiliotherapyâÂÂNew Opportunity for Targeted Therapy in Autosomal Dominant Polycystic Kidney Disease.","authors":"K. Skalická, L. Kovács","doi":"10.4172/2157-7412.1000310","DOIUrl":"https://doi.org/10.4172/2157-7412.1000310","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease which affects nearly 12 million people in the world. Despite the intensive development of new treatment options, hemodialysis and renal replacement therapy remain the only effective treatment of the end-stage disease. However, recently there has been a significant progress in understanding the molecular pathogenesis of the disease, including the discovery of the role of the primary cilium. Recent studies have unequivocally confirmed that the change in the length of the primary cilium is an important trigger of pathological processes that results in the development and progression of ADPKD. The resumption of the primary cilium length by pharmacological regulation can stop cystic growth, prevent fibrosis, and improve kidney function. These results have opened a new era in the development of targeted drugs, so-called ciliotherapy. Early pre-clinical testing of new potential agents has brought promising results. However, there are many challenges in drug development and design of clinical trials in ADPKD, which must be overcome. This review summarized the state of knowledge about the key aspects of the primary cilium in pathogenesis of ADPKD and introduces the latest information on novel compounds that have a great potential in suppressing the development and progression of the disease.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"24 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2016-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72703061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-10-25DOI: 10.4172/2157-7412.1000309
M. Deepika, T. Sunitha, B. Srinadh, K. R. Prasoona, M. Sujatha, A. Ramaiah, A. Jyothy, P. Nallari
Ultrasound imaging serves as a powerful tool in the diagnosis of fetal anomalies. The three and four dimensional ultrasound scan overcomes some of the key limitations related to two-dimensional imaging. It facilitates detailed evaluation of suspected fetal abnormalities of face, neural tube, heart, skeletal and many subtle birth defects, which is pertinent to the pediatric surgeon for timely intervention. It also determines the age and developmental stage of the fetus, detects location and abnormalities of placenta, spot abnormal bleeding, ectopic pregnancies. The present article describes the three rare syndromes Meckel Gruber Syndrome, Holt Oram Syndrome (HOS) and Emanuel syndrome identified. During an attempt to screen a total of 3000 high risk pregnant women for the presence of congenital anomalies by 3D/4D sonography prenatally. Disruption of genes due to deletions and translocation are also identified which could be the putative candidate genes in the syndrome onset.
{"title":"Prenatal assessment of Three Rare Syndromes from Telangana region by 3D/4D Sonography","authors":"M. Deepika, T. Sunitha, B. Srinadh, K. R. Prasoona, M. Sujatha, A. Ramaiah, A. Jyothy, P. Nallari","doi":"10.4172/2157-7412.1000309","DOIUrl":"https://doi.org/10.4172/2157-7412.1000309","url":null,"abstract":"Ultrasound imaging serves as a powerful tool in the diagnosis of fetal anomalies. The three and four dimensional ultrasound scan overcomes some of the key limitations related to two-dimensional imaging. It facilitates detailed evaluation of suspected fetal abnormalities of face, neural tube, heart, skeletal and many subtle birth defects, which is pertinent to the pediatric surgeon for timely intervention. It also determines the age and developmental stage of the fetus, detects location and abnormalities of placenta, spot abnormal bleeding, ectopic pregnancies. The present article describes the three rare syndromes Meckel Gruber Syndrome, Holt Oram Syndrome (HOS) and Emanuel syndrome identified. During an attempt to screen a total of 3000 high risk pregnant women for the presence of congenital anomalies by 3D/4D sonography prenatally. Disruption of genes due to deletions and translocation are also identified which could be the putative candidate genes in the syndrome onset.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"119 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2016-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86759547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-10-20DOI: 10.4172/2157-7412.1000308
E. Pedone, E. Notomista, S. Galdiero, M. Varcamonti, P. Contursi
More than 90% of lung infections in cystic fibrosis (CF) patients are caused by Pseudomonas aeruginosa [1]; further CF pathogens include clinical isolates of Burkholderia cepacia, Staphylococcus aureus and Stenotrophomonas maltophilia, a newly emerging pathogen [2]. Current therapies are targeted at reducing obstruction, inflammation, or infection, but pathogenic bacteria easily develop resistance to conventional antibiotics [3]. Such molecules affect vital microbial functions through recognition and interaction with specific targets involved in metabolic reactions within cells. The susceptibility of these target molecules to mutations makes it easy for the microbes to become resistant to antibiotics. This strongly encourages the quest of novel antimicrobials especially for the treatment of chronic infections.
{"title":"A trans-kingdom antimicrobial peptide targeting cystic fibrosis pathogens","authors":"E. Pedone, E. Notomista, S. Galdiero, M. Varcamonti, P. Contursi","doi":"10.4172/2157-7412.1000308","DOIUrl":"https://doi.org/10.4172/2157-7412.1000308","url":null,"abstract":"More than 90% of lung infections in cystic fibrosis (CF) patients are caused by Pseudomonas aeruginosa [1]; further CF pathogens include clinical isolates of Burkholderia cepacia, Staphylococcus aureus and Stenotrophomonas maltophilia, a newly emerging pathogen [2]. Current therapies are targeted at reducing obstruction, inflammation, or infection, but pathogenic bacteria easily develop resistance to conventional antibiotics [3]. Such molecules affect vital microbial functions through recognition and interaction with specific targets involved in metabolic reactions within cells. The susceptibility of these target molecules to mutations makes it easy for the microbes to become resistant to antibiotics. This strongly encourages the quest of novel antimicrobials especially for the treatment of chronic infections.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"8 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2016-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87880215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-09-19DOI: 10.4172/2157-7412.1000307
Mucciolo Mafalda, C. D. Marco, R. Canitano, S. Buoni, E. Frullanti, M. Mencarelli, Bizzarri Veronica, Sonia Amabile, Lucia Radice, M. Baldassarri, C. L. Rizzo, I. Meloni, J. Hayek, Aless, ra Renieri, F. Mari
Background: Autism Spectrum Disorders (ASD) and Intellectual Disability (ID) represent lifelong conditions with severe impact on behavior and lifestyle of patients and their families. Array comparative genomic hybridization (array-CGH) has clarified the underlying genetic causes of ASD and ID by CNVs identification in several chromosomal regions with susceptibility to different levels of severity of ASD or ID in up to 1% of patients. Methods: Using oligo array-CGH we analyzed 476 unrelated subjects with ASD or ID, thoroughly investigated by both child neuropsychiatrists and clinical geneticists. The inheritance of the CNV were tested in the majority of cases (82% of positive cases). Results: A total of 198 rearrangements was identified in 154 cases. CNVs were classified in three groups: i- CNVs previously known to be associated with ASD or ID (28/198, 14%), including 16p11.2, 15q13.3, 17p12 and 17q12; ii- CNVs including genes known to be associated with either ASD or ID (9/198, 4.5%); iii- CNVs of unknown significance (161/198, 81.3%). Conclusions: Our study confirmed that array-CGH analysis is able to detect the underlying genetic cause in about 18% of ASD or ID patients, highlighting it as an essential diagnostic tool for patients assessment. Overall, a prevalence of duplications with respect to deletions was observed (62% and 38% respectively) but among the deleted cases an enrichment of microdeletions in ASD cases (p=0.03) is present. Furthermore, we shown a prevalence of multiple CNVs in ASD cases compared to ID (p=0.05), pointing out the complex nature of ASD.
{"title":"A Genome Wide Copy Number Variations Analysis in Autism Spectrum Disorder (Asd) and Intellectual Disability (Id) in Italian Families","authors":"Mucciolo Mafalda, C. D. Marco, R. Canitano, S. Buoni, E. Frullanti, M. Mencarelli, Bizzarri Veronica, Sonia Amabile, Lucia Radice, M. Baldassarri, C. L. Rizzo, I. Meloni, J. Hayek, Aless, ra Renieri, F. Mari","doi":"10.4172/2157-7412.1000307","DOIUrl":"https://doi.org/10.4172/2157-7412.1000307","url":null,"abstract":"Background: Autism Spectrum Disorders (ASD) and Intellectual Disability (ID) represent lifelong conditions with severe impact on behavior and lifestyle of patients and their families. Array comparative genomic hybridization (array-CGH) has clarified the underlying genetic causes of ASD and ID by CNVs identification in several chromosomal regions with susceptibility to different levels of severity of ASD or ID in up to 1% of patients. Methods: Using oligo array-CGH we analyzed 476 unrelated subjects with ASD or ID, thoroughly investigated by both child neuropsychiatrists and clinical geneticists. The inheritance of the CNV were tested in the majority of cases (82% of positive cases). Results: A total of 198 rearrangements was identified in 154 cases. CNVs were classified in three groups: i- CNVs previously known to be associated with ASD or ID (28/198, 14%), including 16p11.2, 15q13.3, 17p12 and 17q12; ii- CNVs including genes known to be associated with either ASD or ID (9/198, 4.5%); iii- CNVs of unknown significance (161/198, 81.3%). Conclusions: Our study confirmed that array-CGH analysis is able to detect the underlying genetic cause in about 18% of ASD or ID patients, highlighting it as an essential diagnostic tool for patients assessment. Overall, a prevalence of duplications with respect to deletions was observed (62% and 38% respectively) but among the deleted cases an enrichment of microdeletions in ASD cases (p=0.03) is present. Furthermore, we shown a prevalence of multiple CNVs in ASD cases compared to ID (p=0.05), pointing out the complex nature of ASD.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"23 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77867408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-08-29DOI: 10.4172/2157-7412.1000306
T. M. Pizzato, C. Baptista, E. Martinez, C. Sobreira, A. Mattiello-Sverzut
Objective: To evaluate the performance of boys with DMD in the ten-meter walking test (10MWT) in order to predict gait loss. Method: This longitudinal study consisted of consecutive evaluations, minimum of 3 and maximum of 12, conducted every 4 months, during 33 months, depending on time of inclusion in the study. Ambulant boys with DMD (n=18), ages 4 to 13 yrs, mean 7 (sd=2.22), were assigned to Ambulatory group (A; n=11) or Non-Ambulatory group (NA; n=7) according to their status at the end of the study. Diagnosis was based on the absence of dystrophin in a muscle biopsy and/or identification of a mutation of the dystrophin-gene. The main outcome measures were: 10MWT total time and rates between two consecutive sessions. Secondary measures included: functional status and muscle strength of the hip, knee and ankle. Results: The 10MWT total time for the NA group oscillated over time, while remaining steady for the A group. The NA group showed mean of 16.18 seconds (CI 95% 14.38–17.98) and the A group showed mean of 10.2 seconds (CI 95% 9.08–11.24). The difference between groups was estimated as -5.98 seconds (CI 95%-8.11; -3.89). The linear model of mixed effects identified significant increase in 10MWT time for the NA group and decrease for the A group. The rates were>1.25 for participants who became wheelchair users, indicating increased time to perform 10MWT overtime. Conclusions: Rates ≥ 1.25 indicate the borderline between independent gait and wheelchair confinement and are useful for predicting gait loss.
{"title":"Prediction of Loss of Gait in Duchenne Muscular Dystrophy Using the TenMeter Walking Test Rates","authors":"T. M. Pizzato, C. Baptista, E. Martinez, C. Sobreira, A. Mattiello-Sverzut","doi":"10.4172/2157-7412.1000306","DOIUrl":"https://doi.org/10.4172/2157-7412.1000306","url":null,"abstract":"Objective: To evaluate the performance of boys with DMD in the ten-meter walking test (10MWT) in order to predict gait loss. Method: This longitudinal study consisted of consecutive evaluations, minimum of 3 and maximum of 12, conducted every 4 months, during 33 months, depending on time of inclusion in the study. Ambulant boys with DMD (n=18), ages 4 to 13 yrs, mean 7 (sd=2.22), were assigned to Ambulatory group (A; n=11) or Non-Ambulatory group (NA; n=7) according to their status at the end of the study. Diagnosis was based on the absence of dystrophin in a muscle biopsy and/or identification of a mutation of the dystrophin-gene. The main outcome measures were: 10MWT total time and rates between two consecutive sessions. Secondary measures included: functional status and muscle strength of the hip, knee and ankle. Results: The 10MWT total time for the NA group oscillated over time, while remaining steady for the A group. The NA group showed mean of 16.18 seconds (CI 95% 14.38–17.98) and the A group showed mean of 10.2 seconds (CI 95% 9.08–11.24). The difference between groups was estimated as -5.98 seconds (CI 95%-8.11; -3.89). The linear model of mixed effects identified significant increase in 10MWT time for the NA group and decrease for the A group. The rates were>1.25 for participants who became wheelchair users, indicating increased time to perform 10MWT overtime. Conclusions: Rates ≥ 1.25 indicate the borderline between independent gait and wheelchair confinement and are useful for predicting gait loss.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"93 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85828065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-08-26DOI: 10.4172/2157-7412.1000305
Cristina Oliveira
Purpose Children with Down syndrome present particular characteristics from the diagnosis, specially hands with particularities like regarding size, strength, folds, among other features. Such characteristics can affect the functional performance in relation to manual skills. This study aims to check the scientific literature available in digital media studies on children and adolescents with Down syndrome from 0 to 17 years of age who have undergone evaluation aiming to improve manual dexterity ability. Methods The methodology consisted of extensive research conducted in the last 10 years of scientific literature with the approach of the above theme, selected from LILACS, MEDLINE, SciELO, PubMed, Scopus described according to pre-defined DeCS and Mesh: manual dexterity, fine hand skills, fine motor skills, Down syndrome, evolution and intervention. Results Only eight articles addressing manual dexterity assessment in children with Down syndrome were found, however not all of them presented appropriate tools for fine motor skills evaluation. Conclusion There are few studies related to the theme comprising this population. More specific evaluation studies and intervention should be developed with this population, because these children and adolescents present slower manual dexterity, when compared to typical children.
{"title":"Manual Dexterity of Children and Adolescents with Down Syndrome:Systematic Review of the Literature","authors":"Cristina Oliveira","doi":"10.4172/2157-7412.1000305","DOIUrl":"https://doi.org/10.4172/2157-7412.1000305","url":null,"abstract":"Purpose Children with Down syndrome present particular characteristics from the diagnosis, specially hands with particularities like regarding size, strength, folds, among other features. Such characteristics can affect the functional performance in relation to manual skills. This study aims to check the scientific literature available in digital media studies on children and adolescents with Down syndrome from 0 to 17 years of age who have undergone evaluation aiming to improve manual dexterity ability. Methods The methodology consisted of extensive research conducted in the last 10 years of scientific literature with the approach of the above theme, selected from LILACS, MEDLINE, SciELO, PubMed, Scopus described according to pre-defined DeCS and Mesh: manual dexterity, fine hand skills, fine motor skills, Down syndrome, evolution and intervention. Results Only eight articles addressing manual dexterity assessment in children with Down syndrome were found, however not all of them presented appropriate tools for fine motor skills evaluation. Conclusion There are few studies related to the theme comprising this population. More specific evaluation studies and intervention should be developed with this population, because these children and adolescents present slower manual dexterity, when compared to typical children.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"37 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2016-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86567168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-08-19DOI: 10.4172/2157-7412.1000313
K. McCallum, A. Elbanna, M. Ennis, B. Schock
Cystic Fibrosis (CF) is characterised by prolonged and exaggerated airways inflammation. Despite recent developments to overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator); there is still an unmet need to reduce the inflammatory response. The NF-i«B regulator A20 is a key target to normalise the inflammatory response and is reduced in CF. Here, we describe the plethora of functions of A20 as they apply to innate immune function within the airways. Pharmacological compounds can enhance A20 mRNA and protein expression, but we observed a blunted effect in CF primary epithelial cells. In CF cells pre-treatment with gibberellic acid (GA3) shows anti-inflammatory effects only in some patients. We show that cells with higher basal p38 expression respond with an increase in pro-inflammatory cytokines. Furthermore, all CF PNECs show increased p38 mRNA when stimulated in the presence of GA3. Our results suggest that those patients may benefit from therapeutics targeting p38.
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