Accessible FSHD diagnostics through epigenetic analysis
通过表观遗传分析进行 FSHD 诊断
基本信息
- 批准号:10556422
- 负责人:
- 金额:$ 19.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:4q35AddressAdultAffectAgeBiological AssayBloodCLIA certifiedChildChromosomesChronicClinicalClinical TrialsCollaborationsCommunitiesComplexComputer softwareConsumptionD4Z4DNADNA MethylationDevelopmentDiagnosisDiagnosticDiagnostic testsDideoxy Chain Termination DNA SequencingDiseaseEpigenetic ProcessEthnic PopulationEvaluationFacioscapulohumeral Muscular DystrophyFamilyFamily memberFemaleGenerationsGenesGenomic DNAIndividualInjuryKnowledgeLaboratoriesLifeLimb structureMethodologyModificationMolecular WeightMotorMuscular DystrophiesMyopathyNatural HistoryNeurologistNeuromuscular DiseasesOutcomeParticipantPatientsPenetrancePersonsPopulationPopulations at RiskPrevalencePrognostic MarkerProtocols documentationRunningSalivaSamplingSeveritiesSiteSourceSymptomsTechniquesTestingTimeUnderserved PopulationValidationWorkanalysis pipelineautosomeclinical diagnosisclinical outcome measurescostdiagnostic biomarkerexome sequencinggenetic testingmalemeetingsmembernext generation sequencingnovel diagnosticspatient stratificationpermissivenessprognostic signatureprognostic valueresearch clinical testingsaliva sampletargeted sequencingunderserved community
项目摘要
SUMMARY
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease
that affects males and females of all ages. FSHD is thought to be the third most prevalent
muscular dystrophy (~12:100,000 adults); however, due to variable severity and complications
with genetic testing, many people remain undiagnosed and the prevalence may be significantly
higher. The clinical diagnosis of FSHD by a neurologist can be complicated by the variability of
disease presentation, and is often misdiagnosed as a limb-girdle type muscular dystrophy or a
simple chronic injury. Standard genetic testing for neuromuscular disease using gene-specific
targeted sequencing panels or even whole exome sequencing does not identify FSHD1
(representing >95% of FSHD cases) and can easily miss FSHD2 (<5% of cases). Following
clinical diagnosis, genetic testing is expensive and not accessible to many populations. Thus,
due to a combination of late onset, slow progression of weakness, highly variable clinical
presentation, and lack of access to or knowledge of specific genetic testing, many FSHD
individuals remain undiagnosed for years and the disease runs through families, affecting
multiple members across several generations. In addition, since current genetic testing for
FSHD is costly, time-consuming, complex, incomplete, and incompatible with standard genetic
testing techniques for other neuromuscular diseases, we know very little about the prevalence of
FSHD in many parts of the world as well as in certain ethnic and underserved populations even
within the US. To address this need, we recently developed a novel diagnostic test for all forms
of FSHD based on the epigenetic status of the disease locus. This analysis can be performed
on genomic DNA from any source, including saliva, and of almost any quality, thereby making it
widely available and accessible to family members of any age and people around the world in
underserved communities. Here, we will convert the current diagnostic protocol from low-
throughput single use to a high-throughput next-generation sequencing protocol. This transition
will greatly reduce the cost of the assay and render it more amenable to meeting CLIA approval.
In addition, we are collaborating with the MOVE FSHD study and performing epigenetic analysis
on all 250 participants. These subjects will have in-depth clinical evaluations and documented
natural histories which will allow us to determine if epigenetic profiles of the disease locus can
serve as a prognostic biomarker for FSHD.
总结
面肩肱型肌营养不良症是一种常染色体显性遗传性肌肉疾病
影响所有年龄段的男性和女性。FSHD被认为是第三大流行病
肌营养不良症(约12:100,000成人);然而,由于不同的严重程度和并发症,
通过基因检测,许多人仍然没有被诊断出来,患病率可能会显着增加。
高神经科医生对FSHD的临床诊断可能会因以下因素的变化而复杂化:
疾病的表现,并经常被误诊为肢带型肌营养不良症或
简单的慢性损伤神经肌肉疾病的标准基因检测使用基因特异性
靶向测序板或甚至整个外显子组测序不能鉴定FSHD 1
(代表>95%的FSHD病例)并且可以容易地错过FSHD 2(<5%的病例)。以下
临床诊断,基因检测是昂贵的,许多人无法获得。因此,在本发明中,
由于迟发性、缓慢进展的虚弱、高度可变的临床
介绍,以及缺乏获得或特定基因检测的知识,许多FSHD
个人多年未被诊断,疾病通过家庭传播,
几代人中的多个成员。此外,由于目前的基因检测
FSHD是昂贵的、耗时的、复杂的、不完整的,并且与标准遗传学不相容。
其他神经肌肉疾病的测试技术,我们对患病率知之甚少,
在世界许多地方,以及某些种族和服务不足的人群中,
在美国境内。为了满足这一需求,我们最近开发了一种新的诊断测试,
FSHD基于疾病位点的表观遗传状态。该分析可以通过
来自任何来源的基因组DNA,包括唾液,几乎任何质量,从而使其
广泛提供给任何年龄的家庭成员和世界各地的人们,
服务不足的社区。在这里,我们将把当前的诊断协议从低-
从单次使用的高通量到高通量的下一代测序方案。这一过渡
将大大降低测定的成本,并使其更易于满足CLIA批准。
此外,我们正在与MOVE FSHD研究合作,并进行表观遗传分析。
250名参与者。这些受试者将接受深入的临床评价,并记录
自然史,这将使我们能够确定疾病位点的表观遗传谱是否可以
作为FSHD的预后生物标志物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Peter L Jones其他文献
Engineered telomeres in transgenic Xenopus laevis
转基因非洲爪蟾的工程端粒
- DOI:
10.1007/s11248-007-9076-0 - 发表时间:
2007 - 期刊:
- 影响因子:3
- 作者:
R. Wuebbles;Peter L Jones - 通讯作者:
Peter L Jones
Purification of MeCP2-containing deacetylase from Xenopus laevis.
从非洲爪蟾中纯化含有 MeCP2 的脱乙酰酶。
- DOI:
10.1385/1-59259-182-5:131 - 发表时间:
2002 - 期刊:
- 影响因子:0
- 作者:
Peter L Jones;P. Wade;A. Wolffe - 通讯作者:
A. Wolffe
Validation of the association between MRI and gene signatures in facioscapulohumeral dystrophy muscle: implications for clinical trial design
面肩肱肌营养不良症 MRI 与基因特征之间关联的验证:对临床试验设计的影响
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Chao;S. Friedman;L. Snider;S. R. Bennett;T. Jones;Peter L Jones;Dennis Shaw;S. Blemker;Lara I. Riem;Olivia DuCharme;R. Lemmers;S. M. van der Maarel;Leo H. Wang;R. Tawil;J. Statland;S. Tapscott - 通讯作者:
S. Tapscott
Programming the Transcriptional State of Replicating Methylated DNA*
对复制甲基化 DNA 的转录状态进行编程*
- DOI:
10.1074/jbc.m010967200 - 发表时间:
2001 - 期刊:
- 影响因子:0
- 作者:
W. Stünkel;S. Ait;Peter L Jones;A. Wolffe - 通讯作者:
A. Wolffe
Facioscapulohumeral muscular dystrophy region gene 1 (FRG1) is a dynamic RNA-associated and actin bundling protein
面肩肱型肌营养不良症区域基因 1 (FRG1) 是一种动态 RNA 相关和肌动蛋白捆绑蛋白
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
C. Sun;S. Koningsbruggen;Steven W. Long;Kirsten;Straasheijm;R. Klooster;T. Jones;M. Bellini;L. Lévesque;William;M. Brieher;S. M. V. D. Maarel;Peter L Jones - 通讯作者:
Peter L Jones
Peter L Jones的其他文献
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{{ truncateString('Peter L Jones', 18)}}的其他基金
Accessible FSHD diagnostics through epigenetic analysis
通过表观遗传分析进行 FSHD 诊断
- 批准号:
10391097 - 财政年份:2022
- 资助金额:
$ 19.4万 - 项目类别:
Pathogenic Mechanisms in Facioscapulohumeral Muscular Dystrophy
面肩肱型肌营养不良症的发病机制
- 批准号:
9277391 - 财政年份:2016
- 资助金额:
$ 19.4万 - 项目类别:
Establishing an FSHD-like mouse for therapeutic development
建立类 FSHD 小鼠用于治疗开发
- 批准号:
9167305 - 财政年份:2016
- 资助金额:
$ 19.4万 - 项目类别:
Mechanisms of DUX4 mediated FSHD pathology
DUX4 介导的 FSHD 病理机制
- 批准号:
10554358 - 财政年份:2013
- 资助金额:
$ 19.4万 - 项目类别:
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