PMID- 16170568
OWN - NLM
STAT- MEDLINE
DCOM- 20060814
LR  - 20220129
IS  - 1364-6745 (Print)
IS  - 1364-6745 (Linking)
VI  - 6
IP  - 4
DP  - 2005 Dec
TI  - Homozygosity for the p.K136E mutation in the SLC17A5 gene as cause of an Italian 
      severe Salla disease.
PG  - 195-9
AB  - Lysosomal free sialic acid storage diseases are recessively inherited allelic 
      neurodegenerative disorders that include Salla disease (SD) and infantile sialic 
      acid storage disease (ISSD) caused by mutations in the SLC17A5 gene encoding for 
      a lysosomal membrane protein, sialin, transporting sialic acid from lysosomes. 
      The classical form of SD, enriched in the Finnish population, is related to the 
      p.R39C designed Salla(FIN) founder mutation. A more severe phenotype is due both 
      to compound heterozygosity for the p.R39C mutation and to different mutations. 
      The p.R39C has not been reported in ISSD. We identified the first case of SD 
      caused by the homozygosity for p.K136E (c.406A>G) mutation, showing a severe 
      clinical picture, as demonstrated by the early age at onset, the degree of motor 
      retardation, the occurrence of peripheral nerve involvement, as well as cerebral 
      hypomyelination. Recently, in vitro functional studies have shown that the 
      p.K136E mutant produces a mislocalization and a reduced activity of the 
      intracellular sialin. We discuss the in vivo phenotypic consequence of the 
      p.K136E in relation to the results obtained by the in vitro functional 
      characterization of the p.K136E mutant. The severity of the clinical picture, in 
      comparison with the classical SD, may be explained by the fact that the p.K136E 
      mutation mislocalizes the protein to a greater degree than p.R39C. On the other 
      hand, the presence of a residual transport activity may account for the absence 
      of hepatosplenomegaly, dysostosis multiplex, and early lethality typical of ISSD 
      and related to the abolished transport activity found in this latter form.
FAU - Biancheri, R
AU  - Biancheri R
AD  - Department of Neuroscience and Rehabilitation, Muscular and Neurodegenerative 
      Disease Unit, G. Gaslini Institute, University of Genova, Genova, Italy. 
      roberta@biancheri.com
FAU - Rossi, A
AU  - Rossi A
FAU - Verbeek, H A
AU  - Verbeek HA
FAU - Schot, R
AU  - Schot R
FAU - Corsolini, F
AU  - Corsolini F
FAU - Assereto, S
AU  - Assereto S
FAU - Mancini, G M S
AU  - Mancini GM
FAU - Verheijen, F W
AU  - Verheijen FW
FAU - Minetti, C
AU  - Minetti C
FAU - Filocamo, M
AU  - Filocamo M
LA  - eng
GR  - GTF04002/TI_/Telethon/Italy
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050917
PL  - United States
TA  - Neurogenetics
JT  - Neurogenetics
JID - 9709714
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Symporters)
RN  - 0 (sialic acid transport proteins)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Brain/pathology
MH  - Child, Preschool
MH  - Genotype
MH  - *Homozygote
MH  - Humans
MH  - Italy
MH  - Lysosomes/metabolism
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - *Mutation
MH  - N-Acetylneuraminic Acid/metabolism
MH  - Organic Anion Transporters/*genetics
MH  - Phenotype
MH  - Sialic Acid Storage Disease/*genetics
MH  - Symporters/*genetics
EDAT- 2005/09/20 09:00
MHDA- 2006/08/15 09:00
CRDT- 2005/09/20 09:00
PHST- 2005/06/21 00:00 [received]
PHST- 2005/07/28 00:00 [accepted]
PHST- 2005/09/20 09:00 [pubmed]
PHST- 2006/08/15 09:00 [medline]
PHST- 2005/09/20 09:00 [entrez]
AID - 10.1007/s10048-005-0011-3 [doi]
PST - ppublish
SO  - Neurogenetics. 2005 Dec;6(4):195-9. doi: 10.1007/s10048-005-0011-3. Epub 2005 Sep 
      17.