Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis.

Mutations in the CLN2 gene result in classical late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal childhood neurodegenerative disease. In this report, we present the complete sequence of the human CLN2 gene and define its physical relationship with two other genes that have been previously mapped to chromosome 11p15. The CLN2 gene consists of 13 exons and 12 introns and spans 6.65 kb. By S1 mapping and primer extension, the 5'-terminus of the CLN2 mRNA was mapped to 32 nucleotides upstream of the proposed initiation codon. A number of other elements were found to be located in close proximity to CLN2, including the gene encoding transcription factor TAFII30, the gene encoding intregrin-linked kinase, and an approximately 914-bp fragment that is 82% identical to antithrombin III. In addition, an EST cDNA clone that is transcribed on the strand opposite to CLN2 and that overlaps a portion of the CLN2 gene was identified. Finally, a set of primer pairs are presented for the amplification of the coding sequences, putative promoter, and splice junctions of the CLN2 gene. Taken together, this information will facilitate the molecular analysis of and genetic testing for classical LINCL.