PMID- 10330339
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 6
DP  - 1999 Jun
TI  - Mutational analysis of the defective protease in classic late-infantile neuronal 
      ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.
PG  - 1511-23
AB  - The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a
      progressive and ultimately fatal neurodegenerative disease of childhood. The
      defective gene in this hereditary disorder, CLN2, encodes a recently identified
      lysosomal pepstatin-insensitive acid protease. To better understand the molecular
      pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families.
      In 14 patients, CLN2 protease activities were normal and no mutations were
      identified, suggesting other forms of NCL. Both pathogenic alleles were
      identified in 57 of the other 60 LINCL families studied. In total, 24 mutations
      were associated with LINCL, comprising six splice-junction mutations, 11 missense
      mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide
      insertion. Two mutations were particularly common: an intronic G-->C transversion
      in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a
      C-->T transition in 32 of 115 alleles, which prematurely terminates translation
      at amino acid 208 of 563. An Arg-->His substitution was identified, which was
      associated with a late age at onset and protracted clinical phenotype, in a
      number of other patients originally diagnosed with juvenile NCL.
FAU - Sleat, D E
AU  - Sleat DE
AD  - Center for Advanced Biotechnology and Medicine and Department of Pharmacology,
      University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
      Sleat@waksman.rutgers.edu
FAU - Gin, R M
AU  - Gin RM
FAU - Sohar, I
AU  - Sohar I
FAU - Wisniewski, K
AU  - Wisniewski K
FAU - Sklower-Brooks, S
AU  - Sklower-Brooks S
FAU - Pullarkat, R K
AU  - Pullarkat RK
FAU - Palmer, D N
AU  - Palmer DN
FAU - Lerner, T J
AU  - Lerner TJ
FAU - Boustany, R M
AU  - Boustany RM
FAU - Uldall, P
AU  - Uldall P
FAU - Siakotos, A N
AU  - Siakotos AN
FAU - Donnelly, R J
AU  - Donnelly RJ
FAU - Lobel, P
AU  - Lobel P
LA  - eng
SI  - GENBANK/AF017456
SI  - GENBANK/AF111172
SI  - GENBANK/AJ011912
SI  - GENBANK/D37970
SI  - GENBANK/D83740
SI  - GENBANK/L76740
SI  - GENBANK/U27540
SI  - GENBANK/X64708
SI  - GENBANK/Y08256
GR  - DK45992/DK/NIDDK NIH HHS/United States
GR  - NS37918/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Biomarkers)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.- (Serine Proteases)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases)
RN  - EC 3.4.14.9 (tripeptidyl-peptidase 1)
SB  - IM
EIN - Am J Hum Genet. 2004 Dec;75(6):1158
MH  - Amino Acid Sequence
MH  - Aminopeptidases
MH  - Biomarkers
MH  - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
MH  - Endopeptidases
MH  - Genotype
MH  - Humans
MH  - Infant
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Neuronal Ceroid-Lipofuscinoses/enzymology/*genetics
MH  - Peptide Hydrolases/*genetics
MH  - Polymorphism, Genetic
MH  - Sequence Homology, Amino Acid
MH  - Serine Proteases
PMC - PMC1377895
EDAT- 1999/05/20 06:00
MHDA- 2000/03/21 09:00
CRDT- 1999/05/20 06:00
PHST- 1999/05/20 06:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/05/20 06:00 [entrez]
AID - S0002-9297(07)63654-4 [pii]
AID - 10.1086/302427 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Jun;64(6):1511-23. doi: 10.1086/302427.