MOLECULAR SCREENING OF BATTEN-DISEASE - IDENTIFICATION OF A MISSENSE MUTATION (E295K) IN THE CLN3 GENE

Batten disease, the juvenile form of neuronal ceroid lipofuscinosis, i s a prevalent neuron degenerative disorder of childhood. A 1.02-kb gen omic deletion in the Batten disease gene CLN3 has been determined to b e a common mutation. We developed a PCR method to screen for this dele tion and tested 43 Batten disease probands. We found 36% (31/86) of Ba tten disease chromosomes did not carry the 1.02-kb deletion. Of the th ree heterozygotes for the 1.02-kb deletion, a novel G-to-A missense mu tation at nucleotide 1020 of the CLN3 cDNA sequence was found on two o f the non-1.02-kb deletion chromosomes. The missense mutation resulted in a substitution of glutamic acid (E) by lysine (K) at position 295 (E295 K). The E295 K mutation causes a change in predicted local prote in conformation. This glutamic acid is a highly conserved acidic amino acid, being present in human, mouse, dog and yeast, which suggests it may play an important role in the function of the Batten disease prot ein.