Abstract
The candidate gene for Mucopolysaccharidosis (MPS) type IIIC has been localized to the pericentric region of the chromosome 8 by the linkage disequilibrium analysis. To validate the localization of the gene, we rescued the deficient acetyl-coenzyme A: α-glucosaminide-N-acetylytransferase activity in the cultured cells of MPS IIIC patients by functional complementation via microcell-mediated chromosome transfer. The introduction of the target human monochromosome completely restored the activity confirming functional localization of the candidate gene on human chromosome 8.
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References
Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA (2003) Mutations in COX10 result in a defect in mitochondrial heme. A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. Hum Mol Genet 12:2693–2702
Ausseil J, Loredo-Osti JC, Verner A, Darmond-Zwaig C, Maire I, Poorthuis B, van Diggelen OP, Hudson TJ, Fujiwara TM, Morgan K, Pshezhetsky AV (2004) Localization of a gene for mucopolysaccharidosis IIIC to the pericentromeric region of chromosome 8. J Med Genet 41:941–945
Bame KJ, Rome LH (1985) Acetyl coenzyme A:alpha-glucosaminide N-acetyltransferase: evidence for a transmembrane acetylation mechanism. J Biol Chem 260:11293–11299
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
He W, Voznyi Ya V, Huijmans JG, Geilen GC, Karpova EA, Dudukina TV, Zaremba J, Van Diggelen OP, Kleijer WJ (1994) Prenatal diagnosis of Sanfilippo disease type C using simple fluorometric enzyme assay. Prenat Diagn 14:17–22
Lochmuller H, Johns T, Shoubridge EA (1999) Expression of the E6 and E7 genes of human papillomavirus (HPV16) extends the life span of human myoblasts. Exp Cell Res 248:186–193
Rome LH, Garvin AJ, Allietta MM, Neufeld EF (1979) Two species of lysosomal organelles in cultured human fibroblasts. Cell 17:143–153
Sanfilippo SJ, Podosin R, Langer Jr LO, Good RA (1963) Mental retardation associated with acid mucopolysacchariduria (heparitin sulfate type). J Pediatr 63:837–838
van der Kamp JJ, Niermeijer MF, von Figura K, Giesberts MA (1981) Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C). Clin Genet 20:152–160
Zaremba J, Kleijer WJ, Huijmans GJ, Poorthuis B, Fidzianska E, Glogowska I (1992) Chromosomes 14 and 21 as possible candidates for mapping the gene for Sanfilippo disease type IIIC. J Med Genet 29:514
Acknowledgments
We thank Dr. Eric A. Shoubridge and Dr. Isle Ogilvie for the help in MTCC studies. We also thank Dr. Andrei Verner and the genotyping facilities of Genome Quebec and McGill University Innovation Center for the assistance in performing the genotyping studies. We thank Manon Baril and Louise L’Écuyer for their technical assistance and Dr. Emmanuel Lemyre for helpful comments. V.S. is a recipient of a postdoctoral fellowship from Sainte-Justine Hospital Research Center and A.V.P is a National Investigator of FRSQ. This study has been partially supported by an operating grant from the Sanfilippo Children’s Research Foundation to A.V.P.
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Seyrantepe, V., Tihy, F. & Pshezhetsky, A.V. The microcell-mediated transfer of human chromosome 8 restores the deficient N-acetylytransferase activity in skin fibroblasts of Mucopolysaccharidosis type IIIC patients. Hum Genet 120, 293–296 (2006). https://doi.org/10.1007/s00439-006-0211-4
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DOI: https://doi.org/10.1007/s00439-006-0211-4