“Atypical” Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era

ABSTRACT Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of inherited lysosomal storage disorders characterized by the intracellular accumulation ceroid-lipofuscin compounds and neurodegeneration. Fourteen genes are currently recognized with disease-causing DNA variants: PPT1/CLN1, TPP1/CLN2, CLN3, DNAJC5/CLN4, CLN5, CLN6, MFSD8/CLN7, CLN8, CTSD/CN10, GRN/CLN11, ATP13A2/CLN12, CTSF/CLN13, KCTD7/CLN14, TBCK/CLN15. In frame Cordoba cohort, we studied N=51 cases. The aim this paper is observational retrospective analysis “atypical” phenotypes. PCR-Sanger sequencing and/or massive exome were used as screening methodology. One CLN1 subject showed an atypical prolonged (P) phenotype null PPT1 activity heterozygous compound genotype: E5 c.451C>T, p.Arg151*/g.6302T>G (I3 c.363-3T>G). Other 11 CLN2 individuals (except one girl) TPP1 decreased around 10% minimum value reference interval in leukocytes saliva. variants E7 c.827A>T, p.Asp276Val I7 c.887-10A>G most prevalent. CLN8 individual congenital combination E2 c.1A>G, p.?/E3 c.792C>G, p.Asn264Lys. Massive was installed methodology for precision diagnosis CLN1, CLN2, A genetic/phenotypic local registry under construction.