The long term aim of this project is to find the gene on chromosome 16 responsible for the juvenile form of Batten disease using the positional cloning approach. Batten disease or ceroid lipofuscinosis is a devastating neurodegenerative disease characterized by progressive blindness, seizures and dementia. In many cell types autofluorescent lipopigment is stored. Inheritance is autosomal recessive. The juvenile form of Batten disease or Spielmeyer-Vogt disease (CLN3) is the most frequent type of ceroid lipofuscinosis. It is linked to markers on chromosome 16. A crucial feature of the positional cloning approach to a gene is the reduction of the chromosomal region where the gene can be and thus minimize the number of 'candidate genes' to be studied. Recently, a deletion of the marker locus which is closely linked to the CLN3 gene has been detected in a Batten patient. By determination of the extent of the deletion, the chromosomal region around CLN3 will be substantially reduced. The chromosomal region defined by the end points of the deletion will be doned in overlapping cosmids and yeast artificial chromosomes, a physical map will be constructed, and expressed sequences (genes) will be identified. It is estimated that at least a number of candidate genes can be identified and analysed within the timespan of this project. Isolation of the gene responsible for the juvenile form of Batten disease will improve opportunities for early diagnosis in families at risk, screening for carriers of the mutation, and will help prevent the birth of affected children. When the gene has been found the pathophysiology of this and possibly other forms of Batten disease can be studied. This research may lead to preventive measures or treatment in patients.
Showing the most recent 10 out of 15 publications
