Compound heterozygous genotype is associated with protracted juvenile neuronal ceroid lipofuscinosis.

We present a clinicopathological study and the first molecular genetic analysis of a family with 2 siblings affected by a rare, protracted form of juvenile neuronal ceroid lipofuscinosis (JNCL). Molecular genetic studies showed that both siblings, in addition to being heterozygous for the 1.02-kb CLN3 deletion, a common mutation in JNCL, also had a G-to-A missense mutation at nucleotide 1,020 of the CLN3 cDNA sequence on the non-1.02-kb deletion chromosomes. This point mutation resulted in a substitution of glutamic acid by lysine at position 295 of the CLN3 protein. Thus, a single point mutation at residue 295 of the CLN3 protein in protracted JNCL may underlie the phenotype in this form, which differs from that in classic JNCL.