Genetic analysis of Batten disease

Batten disease, or neuronal ceroid-lipofuscinosis (CLN) comprises a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurones. The three main childhood varieties--infantile (CLN1), late-infantile (CLN2) and juvenile (CLN3)--manifest autosomal recessive inheritance. The basic biochemical defect remains unknown. The strategy of positional cloning is being pursued to elucidate the molecular basis of Batten disease. The infantile disease locus (CLN1) has been mapped by linkage analysis to human chromosome 1p32, and the juvenile disease locus (CLN3) to human chromosome 16p12. In each case marker loci in strong linkage disequilibrium with the disease loci have been identified. Locus heterogeneity between classical late-infantile CLN (CLN2) and both CLN1 and CLN3 has been demonstrated. Work is in progress to clone CLN1 and CLN3 and to map CLN2. Identification of linked markers has provided a new approach to prenatal diagnosis. The methodology exists for positional cloning of these genes and elucidation of the molecular genetic basis of the ceroid lipofuscinoses.