title: Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene.
abstract: Late infantile neuronal ceroid lipofuscinosis, LINCL, is one of the most common pediatric neurodegenerative disorders. It is caused by mutations in the CLN2 gene, which encodes a lysosomal pepstatin-insensitive peptidase (LPIP). We have identified a novel mutation, T523-1G --> A, by molecular analyses of three unrelated LINCL cases. The mutation was found to affect a 3' intronic splicing acceptor site, resulting in an aberrant mRNA with an insertion of 146 bp of intronic sequence. This causes a frame shift, produces a nonfunctional truncated protein, and results in LINCL.
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Hartikainen
authors.forename: W
authors.initials: W
authors.lastname: Ju
authors.forename: K E
authors.initials: KE
authors.lastname: Wisniewski
authors.forename: D N
authors.initials: DN
authors.lastname: Moroziewicz
authors.forename: A L
authors.initials: AL
authors.lastname: Kaczmarski
authors.forename: L
authors.initials: L
authors.lastname: McLendon
authors.forename: D
authors.initials: D
authors.lastname: Zhong
authors.forename: C T
authors.initials: CT
authors.lastname: Suarez
authors.forename: W T
authors.initials: WT
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Zhong
mesh_terms: D000225:Adenine; D000626:Aminopeptidases; D002648:Child; D002675:Child, Preschool; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D005260:Female; D016368:Frameshift Mutation; D005787:Gene Frequency; D006147:Guanine; D006801:Humans; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D012333:RNA, Messenger; D000091346:Tripeptidyl-Peptidase 1; D006147:Guanine; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human; D000225:Adenine