Introduction Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. Since Variants of Late-Infantile NCLs is not completely disease-specific and most of CLN proteins and their natural substrates are not well characterized, combination of clinical and molecular analysis could be an effective method in diagnosis.

Method We performed NGS on four families with walking instability, seizures, cerebellar atrophy and progressive regression in intelligence and behaviour. The onset ages were around 4 years. Whole exomes of affected families were sequenced on Illumina HiSeq X platform.

Result The disease course of all patients in these four affected families started with ataxia then developed to speech abnormalities and myoclonic epilepsy which led to admission.Homozygous or compound heterozygous mutations in four different disease-causing genes were found within the 4 families. They are inTPP1, CLN5, CLN6 and MFSD8 genes respectively. Novel mutations c.1538+1insATCA in TPP1, c.244G>T and c.892G>A in CLN6, c.554-5A>G in MFSD8 were identified

Conclusion In this study, four novel mutations of LINCLs were discovered, which expanded the variant diversity of LINCLs mutations. In addition, we found the clinical features of Chinese LINCL patient are similar to those of Western patients.