From DEPARTMENT OF BIOSCIENCES AND NUTRITION Karolinska Institutet, Stockholm, Sweden MOLECULAR STUDIES OF DYSLEXIA: REGULATION AND FUNCTION OF DYX1C1

Developmental dyslexia is a specific reading disability characterized by unexpected difficulty in reading and writing despite adequate intelligence, education, normal senses and social environment. It is the most common childhood learning disorder affecting five to ten percent of school age children and it is more common among boys than girls. The core deficit in dyslexia is believed to involve phonological processing, the lowest level of the language system needed for reading. Dyslexia has a neurological basis demonstrated by anatomical and functional brain studies, in which differences have been found in the brains of dyslexic readers compared to normal readers. Subtle disturbances in neuronal migration during early brain development have been suggested to be one of the mechanisms leading to dyslexia. Dyslexia has a complex genetic basis that has been investigated by extensive family, twinand molecular genetic studies. To date, many chromosomal loci, including the nine official dyslexia loci, have been linked to dyslexia, and a number of susceptibility genes within those regions have been identified. At least four of these candidate genes are involved in neuronal migration and brain development, otherwise their function it not well understood. The aim of this thesis was to study the regulation and function of the first dyslexia susceptibility gene DYX1C1. The DYX1C1 gene was identified when it was disrupted by a translocation segregating with dyslexia in one family. Since then, many association studies have supported its role in the etiology of dyslexia and general reading ability. In rodents, embryonic knockdown of Dyx1c1 results in deficits in neuronal migration leading to ectopias in the neocortex and hippocampus, and impairments in performing tasks related to learning and