Pub Date : 2018-10-05DOI: 10.4172/2157-7412-c2-020
pMichael S Wolfep
{"title":"A patient at the table: How partnership with patients improves research and enhances service delivery","authors":"pMichael S Wolfep","doi":"10.4172/2157-7412-c2-020","DOIUrl":"https://doi.org/10.4172/2157-7412-c2-020","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88744184","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 : 2018-06-27DOI: 10.4172/2157-7412-C1-017
L. Bhat
{"title":"Serotonergic targets in the treatment of pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF)","authors":"L. Bhat","doi":"10.4172/2157-7412-C1-017","DOIUrl":"https://doi.org/10.4172/2157-7412-C1-017","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90296327","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 : 2018-06-27DOI: 10.4172/2157-7412-C1-018
Yol, E. V. Bever
Methods: Six cases (3 males, 3 females; mean age at surgery 13.2 years) with arthrogryposis multiplex congenital associated with the characteristic amyoplasia were reviewed: they were operated on for scoliosis at the authors’ Spine Surgery Department between 1987 and 2008. Surgery was performed using the Harrington-Luque instrumentation (2 cases), the Luque system (1), a hybrid segmental technique with hooks and screws (1) and spinal anchoring with pedicle screws (2).
{"title":"Rare diagnosis in disorders/differences of sex development","authors":"Yol, E. V. Bever","doi":"10.4172/2157-7412-C1-018","DOIUrl":"https://doi.org/10.4172/2157-7412-C1-018","url":null,"abstract":"Methods: Six cases (3 males, 3 females; mean age at surgery 13.2 years) with arthrogryposis multiplex congenital associated with the characteristic amyoplasia were reviewed: they were operated on for scoliosis at the authors’ Spine Surgery Department between 1987 and 2008. Surgery was performed using the Harrington-Luque instrumentation (2 cases), the Luque system (1), a hybrid segmental technique with hooks and screws (1) and spinal anchoring with pedicle screws (2).","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74643280","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 : 2018-01-20DOI: 10.4172/2157-7412.1000323
J. Cale, S. Fletcher, S. Wilton
Type-1 fibrillinopathies are a family of connective tissue disorders with major clinical manifestations in the skeletal, ocular and cardiovascular systems. The type-1 fibrillinopathies are caused by mutations in the fibrillin-1 gene (FBN1), which encodes fibrillin-1, a large glycoprotein and a major component of the extracellular matrix microfibrils, providing both structural and regulatory support to connective tissues. The type-1 fibrillinopathies have been associated with over 1800 unique mutations within the FBN1 and demonstrate a wide range of phenotypic variability. This, in conjunction with a number of other factors has impacted on the identification of genotypephenotype correlations, pathogenesis and diagnostic tests for this family of diseases, leaving many open-ended theories. Current standard of care relies heavily on surgical intervention and lifelong use of β-blockers to slow disease progression, with research focused heavily on antagonism of transforming growth factor β, which is known to be dysregulated in patients with FBN1 mutations. Antisense oligonucleotides present a novel therapeutic strategy for the type-1 fibrillinopathies, by mediating the alteration of exon arrangement of both the normal and disease-causing mRNA transcripts, to re-establish the periodicity of fibrillin-1. The induced proteins, while internally truncated, should be homologous and thus be able to form multimer units. This treatment alone or in association with isoform switching, TGF-β antagonism or enhanced/inhibited protein degradation could facilitate the assembly of fibrillin-1 monomers into multimers and consequently a decrease in phenotypic severity. This review presents a basic overview of the past and current knowledge about the spectrum of type-1 fibrillinopathies with a particular focus on Marfan syndrome, as well as presenting novel potential therapeutic strategies.
{"title":"A Review of the Type-1 Fibrillinopathies: Pathophysiology, Diagnosis and Novel Therapeutic Strategies","authors":"J. Cale, S. Fletcher, S. Wilton","doi":"10.4172/2157-7412.1000323","DOIUrl":"https://doi.org/10.4172/2157-7412.1000323","url":null,"abstract":"Type-1 fibrillinopathies are a family of connective tissue disorders with major clinical manifestations in the skeletal, ocular and cardiovascular systems. The type-1 fibrillinopathies are caused by mutations in the fibrillin-1 gene (FBN1), which encodes fibrillin-1, a large glycoprotein and a major component of the extracellular matrix microfibrils, providing both structural and regulatory support to connective tissues. The type-1 fibrillinopathies have been associated with over 1800 unique mutations within the FBN1 and demonstrate a wide range of phenotypic variability. This, in conjunction with a number of other factors has impacted on the identification of genotypephenotype correlations, pathogenesis and diagnostic tests for this family of diseases, leaving many open-ended theories. Current standard of care relies heavily on surgical intervention and lifelong use of β-blockers to slow disease progression, with research focused heavily on antagonism of transforming growth factor β, which is known to be dysregulated in patients with FBN1 mutations. Antisense oligonucleotides present a novel therapeutic strategy for the type-1 fibrillinopathies, by mediating the alteration of exon arrangement of both the normal and disease-causing mRNA transcripts, to re-establish the periodicity of fibrillin-1. The induced proteins, while internally truncated, should be homologous and thus be able to form multimer units. This treatment alone or in association with isoform switching, TGF-β antagonism or enhanced/inhibited protein degradation could facilitate the assembly of fibrillin-1 monomers into multimers and consequently a decrease in phenotypic severity. This review presents a basic overview of the past and current knowledge about the spectrum of type-1 fibrillinopathies with a particular focus on Marfan syndrome, as well as presenting novel potential therapeutic strategies.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":" 42","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2018-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72499572","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 : 2018-01-01DOI: 10.4172/2157-7412-C3-023
pLeslie AtleyGT Berry Se McC, less M YudkoffM Tuchman N Ah Mewp
{"title":"Patient-directed insights on the evolution of treating rare genetic diseases","authors":"pLeslie AtleyGT Berry Se McC, less M YudkoffM Tuchman N Ah Mewp","doi":"10.4172/2157-7412-C3-023","DOIUrl":"https://doi.org/10.4172/2157-7412-C3-023","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"516 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77108592","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 : 2018-01-01DOI: 10.4172/2157-7412-C3-025
D. E. Ouail, F. Bouali, D. S. Ahmed, M. Tebbani
{"title":"Niemann Pick disease, about three cases","authors":"D. E. Ouail, F. Bouali, D. S. Ahmed, M. Tebbani","doi":"10.4172/2157-7412-C3-025","DOIUrl":"https://doi.org/10.4172/2157-7412-C3-025","url":null,"abstract":"","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76952230","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 : 2017-12-20DOI: 10.4172/2157-7412.1000322
S. Asadi
Syndrome Raine, a severe skeletal dysplasia is usually caused the deaths of patients aged newborn. There are reports that patients with a milder form of the disease to live longer and have reached the age of a child. Radiological surveys show an increase in bone density generalized sclerosis and osteoarthritis. Raine syndrome is a very rare hereditary lethal skeletal dysplasia. There are few reports of milder phenotypes in which patients survived until late childhood. Radiologic investigations show increased bone density and osteosclerosis. The increased density of bones in the head and face causes a characteristic dysmorphic feature that include a prominent and narrow forehead, proptosis, a small hypoplastic nose with depressed nasal bridge, mid-face hypoplasia, a triangular mouth, coanal atresia, and intracranial cerebral classification. Osteosclerosis is severe enough and could be mistaken with osteopetrosis. Raine syndrome is a hereditary autosomal recessive disease. Its cause is a homozygous or compound heterozygous mutation in the FAM20C and FAM20A gene. The gene encodes a phosphorylase-kinase which is responsible for biomineralization of the skeleton. Bone density at the base of the skull, causing changes in the craniofacial skeleton, leading to specific dysmorphic signs in the figures. Symptoms of the disease include prominent forehead, proptosis, nasal root sunk, hypoplastic middle part of the face, hypoplastic nose, mouth, triangular, Atresia Cowan and intracranial calcification. Bone density in the disease so that the disease osteopetrosis is wrong. Raine syndrome is an autosomal recessive hereditary disease, which is caused by mutations in the genes is FAM20A and FAM20C. This gene encodes a protein that phosphorylase-kinase activity has been implicated in bio-mineralization. In this study, a patient with Raine syndrome. Molecular analysis of the patient, a homozygous mutation new were identified. Already known about the patient’s Eighteenth in the world.
{"title":"Assessment of Mutation Genetics in FAM20A and FAM20C Genes Induction Syndrome Raine with New Mutation c.977-1T>A","authors":"S. Asadi","doi":"10.4172/2157-7412.1000322","DOIUrl":"https://doi.org/10.4172/2157-7412.1000322","url":null,"abstract":"Syndrome Raine, a severe skeletal dysplasia is usually caused the deaths of patients aged newborn. There are reports that patients with a milder form of the disease to live longer and have reached the age of a child. Radiological surveys show an increase in bone density generalized sclerosis and osteoarthritis. Raine syndrome is a very rare hereditary lethal skeletal dysplasia. There are few reports of milder phenotypes in which patients survived until late childhood. Radiologic investigations show increased bone density and osteosclerosis. The increased density of bones in the head and face causes a characteristic dysmorphic feature that include a prominent and narrow forehead, proptosis, a small hypoplastic nose with depressed nasal bridge, mid-face hypoplasia, a triangular mouth, coanal atresia, and intracranial cerebral classification. Osteosclerosis is severe enough and could be mistaken with osteopetrosis. Raine syndrome is a hereditary autosomal recessive disease. Its cause is a homozygous or compound heterozygous mutation in the FAM20C and FAM20A gene. The gene encodes a phosphorylase-kinase which is responsible for biomineralization of the skeleton. Bone density at the base of the skull, causing changes in the craniofacial skeleton, leading to specific dysmorphic signs in the figures. Symptoms of the disease include prominent forehead, proptosis, nasal root sunk, hypoplastic middle part of the face, hypoplastic nose, mouth, triangular, Atresia Cowan and intracranial calcification. Bone density in the disease so that the disease osteopetrosis is wrong. Raine syndrome is an autosomal recessive hereditary disease, which is caused by mutations in the genes is FAM20A and FAM20C. This gene encodes a protein that phosphorylase-kinase activity has been implicated in bio-mineralization. In this study, a patient with Raine syndrome. Molecular analysis of the patient, a homozygous mutation new were identified. Already known about the patient’s Eighteenth in the world.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"25 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80161285","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 : 2017-12-09DOI: 10.4172/2157-7412.1000321
V. Pandey, A. Tripathi, R. Bhushan, Akhtar Ali, P. Dubey
Genetic diseases in human are associated with congenital disorders and phenotypic traits. A single mutation in a gene can cause physical or mental problems, and sometimes both. Some diseases can be lethal, and there are still no cures for many of them. Socioeconomic burden of rare genetic diseases are increasing worldwide that have been tried to cure using various methods. However, they were not very successful till now. Genome editing technologies over the past few years is providing fast and effective tool to precisely manipulate the genome at specific locations. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated Cas9 (CRISPR/Cas9) system has been using from last few years in the field of biomedical research. CRISPR/Cas9 has advantages in terms of clinical applicability to treat genetic diseases like DMD, Hemophilia, β-Thalassemia and cystic fibrosis etc. and even in some cases this tool has already been successfully applied. Nevertheless, developed technologies for addition or deletion of genes have made notable progress in last few years and demonstrate some promising clinical results. However, several challenges still remain. Here, the latest applications of CRISPR-Cas9 technology in genetic disorders, current challenges and future directions are reviewed and discussed.
{"title":"Application of CRISPR/Cas9 Genome Editing in Genetic Disorders: A Systematic Review Up to Date","authors":"V. Pandey, A. Tripathi, R. Bhushan, Akhtar Ali, P. Dubey","doi":"10.4172/2157-7412.1000321","DOIUrl":"https://doi.org/10.4172/2157-7412.1000321","url":null,"abstract":"Genetic diseases in human are associated with congenital disorders and phenotypic traits. A single mutation in a gene can cause physical or mental problems, and sometimes both. Some diseases can be lethal, and there are still no cures for many of them. Socioeconomic burden of rare genetic diseases are increasing worldwide that have been tried to cure using various methods. However, they were not very successful till now. Genome editing technologies over the past few years is providing fast and effective tool to precisely manipulate the genome at specific locations. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated Cas9 (CRISPR/Cas9) system has been using from last few years in the field of biomedical research. CRISPR/Cas9 has advantages in terms of clinical applicability to treat genetic diseases like DMD, Hemophilia, β-Thalassemia and cystic fibrosis etc. and even in some cases this tool has already been successfully applied. Nevertheless, developed technologies for addition or deletion of genes have made notable progress in last few years and demonstrate some promising clinical results. However, several challenges still remain. Here, the latest applications of CRISPR-Cas9 technology in genetic disorders, current challenges and future directions are reviewed and discussed.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"31 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2017-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85074654","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 : 2017-12-07DOI: 10.4172/2157-7412.1000E-132
K. Venkatachalam
3´-Phoaphoadenosine 5´-Phosphosulfate (PAPS) synthase (PAPSS) of human is comprised of two domains [ATP sulfurylase (ATPS)] and [APS kinase (APSK)]. ATP sulfurylase binds ATP and allows the sulfate anion to attack the alpha-phosphoryl by nucleophilic attack. This allows the elimination of pyrophosphate (PPi) and the formation of phospho-sulfate anhydride bond of APS which is energetically higher (~19 kcal/mol) compared to phospho-phosphate (~7.6 kcal/ mol) nucleotide. However, nature chose to have sulfur as well as phosphorous nucleotide, one serving as a universal cellular energy currency, as well as a donor for phosphorylation. In contrast, PAPS was chosen as a universal donor of sulfuryl group for molecule/ macromolecule modifications and not chosen as an energy source. PPi the eliminated product of ATPS is cleaved into two inorganic phosphates by the ubiquitous pyrophosphatase, a process that can drive the whole reaction of APS formation, to certain degree in the forward direction? with the help of substrate concentration gradient. The energy of ~4 kcal must be invested in balance, to at least reach the equilibrium on the ATPS reaction.
{"title":"The Conundrums of 3'Phoaphoadenosine 5'Phosphosulfate (PAPS) Synthase (PAPSS)","authors":"K. Venkatachalam","doi":"10.4172/2157-7412.1000E-132","DOIUrl":"https://doi.org/10.4172/2157-7412.1000E-132","url":null,"abstract":"3´-Phoaphoadenosine 5´-Phosphosulfate (PAPS) synthase (PAPSS) of human is comprised of two domains [ATP sulfurylase (ATPS)] and [APS kinase (APSK)]. ATP sulfurylase binds ATP and allows the sulfate anion to attack the alpha-phosphoryl by nucleophilic attack. This allows the elimination of pyrophosphate (PPi) and the formation of phospho-sulfate anhydride bond of APS which is energetically higher (~19 kcal/mol) compared to phospho-phosphate (~7.6 kcal/ mol) nucleotide. However, nature chose to have sulfur as well as phosphorous nucleotide, one serving as a universal cellular energy currency, as well as a donor for phosphorylation. In contrast, PAPS was chosen as a universal donor of sulfuryl group for molecule/ macromolecule modifications and not chosen as an energy source. PPi the eliminated product of ATPS is cleaved into two inorganic phosphates by the ubiquitous pyrophosphatase, a process that can drive the whole reaction of APS formation, to certain degree in the forward direction? with the help of substrate concentration gradient. The energy of ~4 kcal must be invested in balance, to at least reach the equilibrium on the ATPS reaction.","PeriodicalId":89584,"journal":{"name":"Journal of genetic syndromes & gene therapy","volume":"1984 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2017-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90343425","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：