Document Detail

A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases.
MedLine Citation:
PMID:  10581036     Owner:  NLM     Status:  MEDLINE    
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.
F W Verheijen; E Verbeek; N Aula; C E Beerens; A C Havelaar; M Joosse; L Peltonen; P Aula; H Galjaard; P J van der Spek; G M Mancini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  23     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  1999-12-20     Completed Date:  1999-12-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  462-5     Citation Subset:  IM    
Department of Clinical Genetics, Erasmus University and Academic Hospital, Erasmus Medical Centre of Rotterdam, Rotterdam, The Netherlands.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AC006302;  AF024691;  AJ387747;  X71355; SWISSPROT/P15365;  P42609;  Q03567
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MeSH Terms
Amino Acid Sequence
Anion Transport Proteins
Base Sequence
Carrier Proteins / chemistry,  genetics*,  metabolism
DNA Primers / genetics
Gene Expression
Genes, Recessive
Ion Transport / genetics*
Models, Molecular
Molecular Sequence Data
Neurodegenerative Diseases / genetics*,  metabolism*
RNA, Messenger / genetics,  metabolism
Sequence Homology, Amino Acid
Sialic Acids / metabolism*
Tissue Distribution
Reg. No./Substance:
0/Anion Transport Proteins; 0/Carrier Proteins; 0/DNA Primers; 0/RNA, Messenger; 0/Sialic Acids

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