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I-cell disease and pseudo-Hurler polydystrophy: Heterozygote detection and characteristics of the altered N-acetyl-glucosamine-phosphotransferase in genetic variants |
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| Authors: | OThomas Mueller Laureen E Little Arnold L Miller Carmen B Lozzio Thomas B Shows |
| Institution: | a Department of Human Genetics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, NY 14263, USA b Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA c Birth Defects and Human Development Center, University of Tennessee Memorial Hospital, Knoxville, TN 37920, USA |
| Abstract: | The human disorders I-cell disease and pseudo-Hurler polydystrophy (also known as mucolipidosis II and III, respectively) are caused by an inherited deficiency of UDP-GlcNAc: lysosomal enzyme precursor GlcNAc-P transferase activity. The most common genetic variants of these diseases (complementation group A) can be identified in homozygotes and heterozygotes using a GlcNAc-P transferase assay with artificial acceptors and commercially available radiochemicals. The kinetic characteristics of the residual GlcNAc-P transferase activity in complementation group A fibroblasts indicates that the low activity is due to a low Vmax. The measured Michaelis-Menten constants for the substrates UDP-GlcNAc and  -methyl mannoside are in the normal range. Homozygotes and heterozygotes of another less common variant of pseudo-Hurler polydystrophy (complementation group C) have normal activity and normal kinetic characteristics with this assay using -methyl mannoside as the acceptor substrate. Several PHP variants with unusual characteristics are discussed. |
| Keywords: | I - Cell disease Pseudo-Hurler polydystrophy Mucolipidoses II and III N-Acetyl-glucosaminyl-phosphotransferase assay Hétérozygote detection |
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