Abstracts

Rationale: Linkage analysis of large families with plays a major role in research on genetics of epilepsy. In this study, a novel allele was identified through possible novel causative loci in a chromosomal interval that is linked to the epilepsy phenotype in a three generation Maltese family. Methods: High density single nucleotide polymorphisims (SNP) genechips were used to perform the linkage analysis. Analysis of the DNA from affected family members identified a linkage interval of about 20cM on chromosome 20 (20q13.32-33) which gave a parametric LOD score of 2.67. Results: The inheritance pattern in the family was found to be autosomal dominant with incomplete penetrance. The linkage interval on chromosome 20 was confirmed using markers for Short Tandem Repeats (STRs). The affected individuals were found to have a different haplotype from the non-affected individuals. A novel 24bp deletion was, in fact, identified in all the affected individuals. This allele was found to normally occur only at a frequency of 0.04 in the general Maltese population. Conclusions: This research has identified a possible novel allele which can contribute to idiopathic epilepsy. Such research contributes to a better understanding the cause of this condition. When considering that 30% of people who have epilepsy are pharmacoresistant, and other affected individuals still have a low quality of life in spite of treatment with antiepileptic drugs, it is imperative that the knowledge gained though genetic studies is used in the identification of novel therapeutic targets and the development of new drugs.