MD, PhD student Section Neuromuscular Diseases
Department of Neurology and Neurosurgery
email
m.a.vanes@umcutrecht.nltel +31-88 75 56506
ProjectGenetics of ALS
Supervisors
L.H.Van den Berg
Aims of project
- Identify all cases and compile complete pedigrees of familial ALS (fALS) in The Netherlands and determine phenotype, prevalence of fALS, SOD1 and VAPB mutations in The Netherlands. Finally, DNA will be collected and stored for future linkage analysis.
- Perform a genome wide association study to identify genes involved in the pathogenesis of sporadic ALS in The Netherlands.
Summary
ALS is characterised by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS can occur at any age, with a median onset in the mid- fifties. Approximately 50% of the patients die within 3-4 years after the diagnosis. Respiratory failure by paralysis of respiratory muscles, is the most common cause of death. In +/- 10 % of patients, ALS occurs in families (familial ALS (fALS)). In most populations mutations in the copper/zinc superoxide dismutase (SOD1) gene were observed in about 20 % of fALS patients. A second mutation in the VAPB has recently been identified in a large kindred in Brazil. In contrast, we have observed that mutations in the SOD1 gene are very rare in fALS in the Netherlands, indicating a unique genetic background. Systemic studies on the relative frequency of FALS, mode of inheritance, phenotype, relative frequency of SOD1 and VAPB mutations are not available for the Netherlands. Sporadic ALS (sALS) is a complex disease in which genetic and environmental factors are involved in the pathogenesis. We will perform a genome wide association study in 500 cases of sALS and 500 controls in the Netherlands, followed by a second replication study in an independent similar Dutch sample. Our goal is to identify sequence variants involved in the pathogenesis in sALS in the Netherlands.