Genetic analysis in families with neurological disease

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

The identification of gene mutations causing disease lends new insight into the pathogenesis and etiology of the disorder under examination. We have identified mutation of ITPR1, TTBK2 and duplication of a segment on chromosome 11 as causes of spinocerebellar ataxia (SCA11, SCA15 and SCA20). We have also defined a novel locus for hereditary spastic paraplegia on chromosome 19. Much of the current work seeks to expand upon this effort, characterizing the frequency and clinical range of these mutations. We continue to investigate families without known mutations including rare families with parkinsonism, dystonia and ataxia, by genome wide SNP mapping and most recently by deep sequencing. We have recently completed a project to define mutations in Brown Vialleto Van Laere syndrome using exome sequencing;and have identified the mutation underlying this disease in 2 families. Collecting and working on families with neurological disease continues to be a focus of the laboratory, and we have paid particular attention to rare apparently recessive forms of disease, including ataxia, dementia and parkinson's disease. Using current high throughput sequencing we are in the early stages of gene prioritization for each of these disorders.