Heterogeneity of late-infantile neuronal ceroid lipofuscinosis

Purpose: Late-infantile neuronal ceroid lipofuscinosis (LINCL), an autosoma l recessively inherited lysosomal storage disorder characterized by autoflu orescent inclusions and rapid progression of neurodegeneration, is due to C LN2 gene mutations. However, CLN2 mutation analysis has failed to identify some clinically diagnosed "late-infantile" NCL cases. This study was conduc ted to further characterize genetic heterogeneity in families affected by L INCL. Methods: DNA mutations in the CLN1, CLN2, and CLN3 genes that underli e INCL (infantile NCL), LINCL, and JNCL (juvenile NCL), respectively, were studied with molecular analyses. Results: A total of 252 families affected by childhood NCL were studied. Of 109 families clinically diagnosed as havi ng LINCL, 3 were determined to have either INCL or JNCL by identification o f mutation(s) in CLN1 or CLN3. Six families diagnosed initially as having J NCL were found to have LINCL based on the finding of mutations in the CLN2 gene. In addition, several novel mutations were identified. Conclusions: Cl inical and genetic heterogeneity of LINCL was demonstrated in nine LINCL fa milies studied.