R. Seppala et al., Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define thedisease sialuria and the allosteric site of the enzyme, AM J HU GEN, 64(6), 1999, pp. 1563-1569
Citations number
27
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Sialuria is a rare inborn error of metabolism characterized by cytoplasmic
accumulation and increased urinary excretion of free N-acetylneuraminic aci
d (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from
loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epi
merase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-N-acetylneuramini
c acid (CMP-Neu5Ac). We report the cloning and characterization of human UD
P-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with si
aluria. Their heterozygote mutations, R266W; R266Q, and R263L, indicate tha
t the allosteric site of the epimerase resides in the region of codons 263-
266. The heterozygous nature of the mutant allele in all three patients rev
eals a dominant mechanism of inheritance for sialuria.