Studies Of Hereditary Neurological Disease: Disease Gene Identification

遗传性神经疾病的研究：疾病基因鉴定

• 批准号: 9563109
• 负责人: Kenneth Fischbeck
• 金额: $ 61.6万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9563109
• 关键词: Africa; Africa South of the Sahara; Biology; Candidate Disease Gene; Collaborations; Consanguinity; DNA sequencing; Developing Countries; Diagnosis; Disease; Distal; Family; Genes; Genetic; Genetic study; Genomics; Goals; Hereditary Spastic Paraplegia; Individual; Inherited; Mali; Missense Mutation; Muscular Atrophy; Neurodegenerative Disorders; Neuromuscular Diseases; Patients; Phenotype; Procedures; Reporting; Research; Sensory; Single Nucleotide Polymorphism; Testing; base; consanguineous family; cost; effective therapy; exome sequencing; genetic disorder diagnosis; interest; nervous system disorder; novel; outreach program; programs; segregation

The purpose of this research program is to investigate the causes of hereditary neurological diseases, with the goal of developing effective treatments for these disorders. A genetic outreach program allows the identification and characterization of patients and families with hereditary neurological diseases. Specific research accomplishments in the past year include collaboration in genetic studies in Mali and in a review of procedures for reporting of secondary genomic findings from exome sequencing. Through the Mali collaboration, over 120 families have been evaluated, with more than 17 different genetic diagnoses in 24 families. Our current focus is on the remaining families with phenotypes of interest, autosomal recessive inheritance & consanguinity. Exome sequencing and segregation analysis are done through NISC for candidate gene identification. We evaluated a Malian family in which three individuals had hereditary spastic paraplegia (HSP) and distal muscle atrophy and sensory loss. HSP panel testing identified a novel heterozygous missense mutation in KIF5A (c.1086G>C, p.Lys362Asn) that segregated with the disease (SPG10). Lys362 is highly conserved across species and Lys362Asn is predicted to be damaging. This study shows that HSPs are present in sub-Saharan Africa, although likely underdiagnosed. Increasing efficiency and decreasing costs of DNA sequencing will make it more feasible to diagnose HSPs in developing countries.

这项研究计划的目的是调查遗传性神经系统疾病的原因，以开发有效的治疗这些疾病的目标。遗传外展计划允许识别和表征遗传神经疾病的患者和家庭。过去一年的具体研究成果包括在马里的遗传研究方面的合作，以及对外显子组测序的次级基因组发现报告程序的审查。