PMID- 10581036
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20061115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 4
DP  - 1999 Dec
TI  - A new gene, encoding an anion transporter, is mutated in sialic acid storage
      diseases.
PG  - 462-5
AB  - Sialic acid storage diseases (SASD, MIM 269920) are autosomal recessive
      neurodegenerative disorders that may present as a severe infantile form (ISSD) or
      a slowly progressive adult form, which is prevalent in Finland (Salla disease).
      The main symptoms are hypotonia, cerebellar ataxia and mental retardation;
      visceromegaly and coarse features are also present in infantile cases.
      Progressive cerebellar atrophy and dysmyelination have been documented by
      magnetic resonance imaging (ref. 4). Enlarged lysosomes are seen on electron
      microscopic studies and patients excrete large amounts of free sialic acid in
      urine. A H+/anionic sugar symporter mechanism for sialic acid and glucuronic acid
      is impaired in lysosomal membranes from Salla and ISSD patients. The locus for
      Salla disease was assigned to a region of approximately 200 kb on chromosome
      6q14-q15 in a linkage study using Finnish families. Salla disease and ISSD were
      further shown to be allelic disorders. A physical map with P1 and PAC clones was 
      constructed to cover the 200-kb area flanked by the loci D6S280 and D6S1622,
      providing the basis for precise physical positioning of the gene. Here we
      describe a new gene, SLC17A5 (also known as AST), encoding a protein (sialin)
      with a predicted transport function that belongs to a family of anion/cation
      symporters (ACS). We found a homozygous SLC17A5 mutation (R39C) in five Finnish
      patients with Salla disease and six different SLC17A5 mutations in six ISSD
      patients of different ethnic origins. Our observations suggest that mutations in 
      SLC17A5 are the primary cause of lysosomal sialic acid storage diseases.
FAU - Verheijen, F W
AU  - Verheijen FW
AD  - Department of Clinical Genetics, Erasmus University and Academic Hospital,
      Erasmus Medical Centre of Rotterdam, Rotterdam, The Netherlands.
      verheijen@ikg.fgg.eur.nl
FAU - Verbeek, E
AU  - Verbeek E
FAU - Aula, N
AU  - Aula N
FAU - Beerens, C E
AU  - Beerens CE
FAU - Havelaar, A C
AU  - Havelaar AC
FAU - Joosse, M
AU  - Joosse M
FAU - Peltonen, L
AU  - Peltonen L
FAU - Aula, P
AU  - Aula P
FAU - Galjaard, H
AU  - Galjaard H
FAU - van der Spek, P J
AU  - van der Spek PJ
FAU - Mancini, G M
AU  - Mancini GM
LA  - eng
SI  - GENBANK/AC006302
SI  - GENBANK/AF024691
SI  - GENBANK/AJ387747
SI  - GENBANK/X71355
SI  - SWISSPROT/P15365
SI  - SWISSPROT/P42609
SI  - SWISSPROT/Q03567
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Anion Transport Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sialic Acids)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Anion Transport Proteins
MH  - Base Sequence
MH  - Carrier Proteins/chemistry/*genetics/metabolism
MH  - DNA Primers/genetics
MH  - Female
MH  - Gene Expression
MH  - Genes, Recessive
MH  - Humans
MH  - Infant
MH  - Ion Transport/*genetics
MH  - Male
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Neurodegenerative Diseases/*genetics/*metabolism
MH  - Pedigree
MH  - RNA, Messenger/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Sialic Acids/*metabolism
MH  - Tissue Distribution
EDAT- 1999/12/02 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/02 09:00
PHST- 1999/12/02 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/02 09:00 [entrez]
AID - 10.1038/70585 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Dec;23(4):462-5. doi: 10.1038/70585.