Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene.
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.
Hartikainen
J M
JM
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
Ju
W
W
Wisniewski
K E
KE
Moroziewicz
D N
DN
Kaczmarski
A L
AL
McLendon
L
L
Zhong
D
D
Suarez
C T
CT
Brown
W T
WT
Zhong
N
N
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
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