PMID- 10508524
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20111117
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 2
DP  - 1999 Oct
TI  - The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are
      associated with mutations in CLN8.
PG  - 233-6
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group
      of progressive neurodegenerative disorders characterized by the accumulation of
      autofluorescent lipopigment in various tissues. Progressive epilepsy with mental 
      retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype
      (CLN8). It is an autosomal recessive disorder characterized by onset of
      generalized seizures between 5 and 10 years, and subsequent progressive mental
      retardation. Here we report the positional cloning of a novel gene, CLN8, which
      is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients
      were homozygous for a missense mutation (70C-->G, R24G) that was not found in
      homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays
      82% nucleotide identity with CLN8, conservation of the codon harbouring the human
      mutation and is localized to the same region as the motor neuron degeneration
      mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we
      identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a
      frameshift and a truncated protein. Our data demonstrate that mutations in these 
      orthologous genes underlie NCL phenotypes in human and mouse, and represent the
      first description of the molecular basis of a naturally occurring animal model
      for NCL.
FAU - Ranta, S
AU  - Ranta S
AD  - Folkhalsan Institute of Genetics, Helsinki, Finland. susanna.ranta@helsinki.fi
FAU - Zhang, Y
AU  - Zhang Y
FAU - Ross, B
AU  - Ross B
FAU - Lonka, L
AU  - Lonka L
FAU - Takkunen, E
AU  - Takkunen E
FAU - Messer, A
AU  - Messer A
FAU - Sharp, J
AU  - Sharp J
FAU - Wheeler, R
AU  - Wheeler R
FAU - Kusumi, K
AU  - Kusumi K
FAU - Mole, S
AU  - Mole S
FAU - Liu, W
AU  - Liu W
FAU - Soares, M B
AU  - Soares MB
FAU - Bonaldo, M F
AU  - Bonaldo MF
FAU - Hirvasniemi, A
AU  - Hirvasniemi A
FAU - de la Chapelle, A
AU  - de la Chapelle A
FAU - Gilliam, T C
AU  - Gilliam TC
FAU - Lehesjoki, A E
AU  - Lehesjoki AE
LA  - eng
SI  - GENBANK/AA368223
SI  - GENBANK/AA515629
SI  - GENBANK/AA563326
SI  - GENBANK/AA765593
SI  - GENBANK/AA771241
SI  - GENBANK/AA807426
SI  - GENBANK/AA921233
SI  - GENBANK/AF123757
SI  - GENBANK/AF123758
SI  - GENBANK/AF123759
SI  - GENBANK/AF123760
SI  - GENBANK/AF123761
SI  - GENBANK/AF125307
SI  - GENBANK/AF125308
SI  - GENBANK/AI246377
GR  - NS29110/NS/NINDS NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
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  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (CLN8 protein, human)
RN  - 0 (Cln8 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Chromosome Mapping
MH  - DNA Mutational Analysis
MH  - Epilepsy/complications/*genetics
MH  - Exons
MH  - Family Health
MH  - Female
MH  - Genes/genetics
MH  - Humans
MH  - Intellectual Disability/complications/*genetics
MH  - Introns
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - Mutagenesis, Insertional
MH  - Mutation
MH  - Neuronal Ceroid-Lipofuscinoses/complications/*genetics
MH  - Pedigree
MH  - Point Mutation
MH  - RNA, Messenger/genetics/metabolism
MH  - Sequence Alignment
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
EDAT- 1999/10/03 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/03 09:00
PHST- 1999/10/03 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/03 09:00 [entrez]
AID - 10.1038/13868 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Oct;23(2):233-6. doi: 10.1038/13868.