PMID- 10947946
OWN - NLM
STAT- MEDLINE
DCOM- 20001031
LR  - 20240412
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 67
IP  - 4
DP  - 2000 Oct
TI  - The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage 
      diseases indicates some genotype-phenotype correlation.
PG  - 832-40
AB  - Lysosomal free sialic acid-storage diseases include the allelic disorders Salla 
      disease (SD) and infantile sialic acid-storage disease (ISSD). The defective 
      gene, SLC17A5, coding for the lysosomal free sialic acid transporter was recently 
      isolated by positional cloning. In the present study, we have identified a large 
      number of mutations in SLC17A5 in patients presenting with either Salla disease 
      or the ISSD phenotype. We also report for the first time the exon-intron 
      boundaries of SLC17A5. All Finnish patients with SD (n=80) had a missense 
      mutation changing a highly conserved arginine to cysteine (R39C); 91% of them 
      were homozygotes for this old founder mutation. The compound-heterozygote 
      patients, with the founder mutation in only one allele, presented with a more 
      severe phenotype than did the homozygote patients. The same R39C mutation was 
      also found both in most of the Swedish patients with SD and in a heterozygous 
      form in five patients from central Europe who presented with an unusually severe 
      (intermediate) SD phenotype. Ten different mutations, including deletions, 
      insertions, and missense and nonsense mutations, were identified in patients with 
      the most severe ISSD phenotype, most of whom were compound heterozygotes. Our 
      results indicate some genotype-phenotype correlation in free sialic acid-storage 
      diseases, suggesting that the phenotype associated with the homozygote R39C 
      mutation is milder than that associated with other mutations.
FAU - Aula, N
AU  - Aula N
AD  - National Public Health Institute, Department of Human Molecular Genetics, 
      Helsinki, Finland.
FAU - Salomaki, P
AU  - Salomaki P
FAU - Timonen, R
AU  - Timonen R
FAU - Verheijen, F
AU  - Verheijen F
FAU - Mancini, G
AU  - Mancini G
FAU - Mansson, J E
AU  - Mansson JE
FAU - Aula, P
AU  - Aula P
FAU - Peltonen, L
AU  - Peltonen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20000817
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (RNA, Messenger)
RN  - 0 (Symporters)
RN  - 0 (sialic acid transport proteins)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Age of Onset
MH  - Alleles
MH  - Amino Acid Substitution/genetics
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Finland/epidemiology
MH  - Founder Effect
MH  - Gene Frequency/genetics
MH  - Genetic Testing
MH  - Heterozygote
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Introns/genetics
MH  - Lysosomal Storage Diseases/epidemiology/*genetics/*metabolism/physiopathology
MH  - Membrane Transport Proteins/chemistry/*genetics
MH  - Mutation/*genetics
MH  - N-Acetylneuraminic Acid/*metabolism
MH  - *Organic Anion Transporters
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Protein Conformation
MH  - RNA, Messenger/analysis/genetics
MH  - Sweden/epidemiology
MH  - *Symporters
PMC - PMC1287888
EDAT- 2000/08/19 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/04/01
CRDT- 2000/08/19 11:00
PHST- 2000/06/12 00:00 [received]
PHST- 2000/07/31 00:00 [accepted]
PHST- 2000/08/19 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/19 11:00 [entrez]
PHST- 2001/04/01 00:00 [pmc-release]
AID - S0002-9297(07)63277-7 [pii]
AID - 002001 [pii]
AID - 10.1086/303077 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2000 Oct;67(4):832-40. doi: 10.1086/303077. Epub 2000 Aug 17.