Inherited Neuropathies

遗传性神经病

• 批准号: 7942662
• 负责人: Stephan Zuchner
• 金额: $ 47.18万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942662
• 关键词: Age; Arts; Blood specimen; Charcot-Marie-Tooth Disease; Chromosome Mapping; Clinical; Clinical Research; Collection; DNA; DNA Library; DNA Resequencing; Diabetic Neuropathies; Disease; Ensure; Exclusion; Family; Functional disorder; Generations; Genes; Genetic; Genomics; Human; Inherited; Institutes; Intervention; Link; Maps; Measures; Mutation; Nerve Degeneration; Neural Conduction; Outcome; Patients; Peripheral Nervous System Diseases; RNA; Rare Diseases; Research Personnel; Resources; Sampling; Schwann Cells; Severities; Technology; Testing; Variant; abstracting; biobank; exome; genetic pedigree; genome wide association study; genome-wide; hereditary neuropathy; innovation; nervous system disorder; next generation; novel; peripheral blood; research clinical testing; tool; trait

ABSTRACT: The various rare forms of hereditary peripheral neuropathies are known as Charcot-Marie-Tooth (CMT) disease and comprise a clinically and genetically heterogeneous set of neurological disorders. Traditionally, the disease is divided into demyelinating CMT1 forms with decreased nerve conduction velocities (NCV) and axonal CMT2 types with normal NCVs. More than 35 different genes have been identified for CMT and include autosomal dominant, recessive and X-linked forms. Still, only 40% of axonal (CMT2) cases currently have a mutation in one of the known genes. Importantly, the degree of phenotypic variation of severity, age-at-onset, and other measures within families is quite remarkable, yet genetic modifying factors have not been identified. Modifying factors in CMT families are likely targets for intervention and may well be important for other non-hereditary peripheral neuropathies, such as diabetic neuropathy. These studies have proven difficult however, primarily due to a lack of collections of patients with consistent clinical evaluations and their DNA. The proposed Rare Diseases Clinical Research Consortia (RDCRC) will substantially enhance our resources and quickly provide a large number of CMT patients and families evaluated with the same clinical severity score. A new generation of genetic tools is now available to tackle these important questions, such as genome-wide association studies and next-generation sequencing technology. These will also be applied to identify additional CMT2 genes in small pedigrees using innovative approaches.

摘要：各种罕见的遗传性周围神经病被称为Charcot-Marie-Tooth (CMT)疾病，包括一组临床和遗传上不同的神经疾病。 传统上，这种疾病被分为脱髓鞘CMT1类型，神经传导速度减慢。 (NCV)和NCVS正常的轴索型CMT2型。有超过35种不同的基因被确定为CMT 包括常染色体显性、隐性和X连锁。尽管如此，只有40%的轴突(CMT2)病例 目前在其中一个已知基因上有突变。重要的是，表型变异的程度 严重程度、发病年龄和家庭内的其他指标是相当显著的，但遗传修饰因素 还没有确定身份。CMT家族中的修饰因素可能是干预的目标，而且很可能是 对其他非遗传性周围神经病变很重要，如糖尿病神经病变。这些研究已经 然而，事实证明这很困难，主要是因为缺乏具有一致临床评估的患者集合 以及他们的DNA。拟议的罕见疾病临床研究联盟(RDCRC)将大大提高 我们的资源和迅速提供的大量CMT患者和家庭评价相同 临床严重度评分。新一代的基因工具现在可以用来解决这些重要的问题， 例如全基因组关联研究和下一代测序技术。这些也将是 应用创新方法在小家系中鉴定额外的CMT2基因。