PMID- 10655055
OWN - NLM
STAT- MEDLINE
DCOM- 20000228
LR  - 20061115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 24
IP  - 2
DP  - 2000 Feb
TI  - ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in
      a new gene encoding an 11.5-kb ORF.
PG  - 120-5
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an 
      early onset neurodegenerative disease with high prevalence (carrier frequency
      1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We
      previously mapped the gene responsible for ARSACS to chromosome 13q11 and
      identified two ancestral haplotypes. Here we report the cloning of this gene,
      SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is
      encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to
      be identified in any vertebrate organism. The ORF is conserved in human and
      mouse. The putative protein contains three large segments with sequence
      similarity to each other and to the predicted protein of an Arabidopsis thaliana 
      ORF. The presence of heat-shock domains suggests a function for sacsin in
      chaperone-mediated protein folding. SACS is expressed in a variety of tissues,
      including the central nervous system. We identified two SACSmutations in ARSACS
      families that lead to protein truncation, consistent with haplotype analysis.
FAU - Engert, J C
AU  - Engert JC
AD  - Montreal Genome Centre, McGill University Health Centre Research Institute,
      Montreal, Quebec, Canada.
FAU - Berube, P
AU  - Berube P
FAU - Mercier, J
AU  - Mercier J
FAU - Dore, C
AU  - Dore C
FAU - Lepage, P
AU  - Lepage P
FAU - Ge, B
AU  - Ge B
FAU - Bouchard, J P
AU  - Bouchard JP
FAU - Mathieu, J
AU  - Mathieu J
FAU - Melancon, S B
AU  - Melancon SB
FAU - Schalling, M
AU  - Schalling M
FAU - Lander, E S
AU  - Lander ES
FAU - Morgan, K
AU  - Morgan K
FAU - Hudson, T J
AU  - Hudson TJ
FAU - Richter, A
AU  - Richter A
LA  - eng
SI  - GENBANK/AB006708
SI  - GENBANK/AF193556
SI  - GENBANK/AF193557
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (SACS protein, human)
RN  - 0 (Sacs protein, mouse)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arabidopsis/genetics
MH  - Ataxia/*genetics
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 13
MH  - Exons
MH  - Heat-Shock Proteins/chemistry/*genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - *Open Reading Frames
MH  - Prevalence
MH  - Quebec/epidemiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Spinocerebellar Degenerations/*genetics
EDAT- 2000/02/02 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
AID - 10.1038/72769 [doi]
PST - ppublish
SO  - Nat Genet. 2000 Feb;24(2):120-5. doi: 10.1038/72769.