title: A novel nonsense mutation (Q509X) in three Italian late-infantile neuronal ceroid-lipofuscinosis children.
abstract: We identified a novel nonsense CLN2 mutation (Q509X) in three Italian children with classical late-infantile neuronal ceroid lipofuscinosis (LINCL) from two unrelated families. The mutation introduced a premature stop codon in exon 12 of the CLN2 gene, resulting in a protein lacking the last 54 residues. Haplotype analysis suggested independent origin of the mutation in our families. The protein truncation test was employed to verify the functional consequences of the novel Q509X mutation. In Patient 1, the mutant alleles were transcribed but translated in a shorted peptide suggesting that the Q509X mutation is likely to interfere with CLN2p function. While expanding the list of genetic variants in LINCL, our findings represent the first molecular characterization of LINCL patients in South Europe.
authors.affiliation: Molecular Medicine & Dept. of Neurosciences, IRCCS-Osp. Bambino Gesù, Rome.
authors.forename: A
authors.initials: A
authors.lastname: Tessa
authors.forename: A
authors.initials: A
authors.lastname: Simonati
authors.forename: A
authors.initials: A
authors.lastname: Tavoni
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000626:Aminopeptidases; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D005260:Female; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D010447:Peptide Hydrolases / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D015415:Biomarkers; D018389:Codon, Nonsense; D018388:Codon, Terminator; D000091346:Tripeptidyl-Peptidase 1; D005973:Glutamine; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human