Annick Raas-Rothschild, Valerie Cormier-Daire, Ming Bao, Emmanuelle Genin, Remi Salomon, Kevin Brewer, Marsha Zeigler, Hanna Mandel, Steve Toth, Bruce Roe, Arnold Munnich, William M. Canfield
J Clin Invest.
2000;
105(5):673–681
doi:10.1172/JCI5826
This article Copyright © 2000, The American Society for Clinical Investigation
Abstract
|
Full text
|
PDF
M
ucolipidosis IIIC, or variant pseudo-Hurler polydystrophy, is an autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (N-Acetylglucosamine-1-phosphotransferase [GlcNAc-phosphotransferase]) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Bovine GlcNAc-phosphotransferase has recently been isolated as a multisubunit enzyme with the subunit structure α2β2γ2. We cloned the cDNA for the human γ-subunit and localized its gene to chromosome 16p. We also showed, in a large multiplex Druze family that exhibits this disorder, that MLIIIC also maps to this chromosomal region. Sequence analysis of the γ-subunit cDNA in patients from 3 families identified a frameshift mutation, in codon 167 of the γ subunit, that segregated with the disease, indicating MLIIIC results from mutations in the phosphotransferase γ-subunit gene. This is to our knowledge the first description of the molecular basis for a human mucolipidosis and suggests that the γ subunit functions in lysosomal hydrolase recognition.
This file is in Adobe Acrobat (PDF) format.
If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not
allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users:
Right-click on the Download link and choose the option that says something like "Save Link As...".
Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you
configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can
usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
