title: [From gene to disease; from CLN1, CLN2 and CLN3 to neuronal ceroid lipofuscinosis].
abstract: The neuronal ceroid lipofuscinoses (NCL) are worldwide the most common lysosomal storage disorders of childhood. Clinical features often include progressive visual impairment, seizures, psychomotor deterioration, dementia, and premature death. Most NCL cases are caused by mutations in the CLN1, CLN2 and CLN3 genes, which play an essential role in lysosomal protein degradation. Laboratory diagnostics for a patient suspected of NCL should start with enzyme analysis in the case of INCL and LINCL and investigation of lymphocyte vacuolisation for JNCL. Diagnosis at the protein level is not available for JNCL, but CLN3 mutation analysis is possible. The carrier status of healthy relatives in families with known mutations in either CLN1, CLN2, CLN3 or CLN6 can be determined with certainty by mutation analysis.
authors.affiliation: Leids Universitair Medisch Centrum, Centrum voor Humane en Klinische Genetica, Postbus 9503, 2300 RA Leiden. p.taschner@lumc.nl
authors.forename: P E M
authors.initials: PE
authors.lastname: Taschner
authors.forename: M
authors.initials: M
authors.lastname: Losekoot
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: I
authors.initials: I
authors.lastname: Hofman
authors.forename: O P
authors.initials: OP
authors.lastname: van Diggelen
mesh_terms: D000626:Aminopeptidases; D002648:Child; D004252:DNA Mutational Analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D057057:Serine Proteases; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human