A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy.
A 47-year-old female who presented with a dilated cardiomyopathy and mild neuropathy was found to have pseudoHurler polydystrophy (mucolipidosis III). The serum lysosomal enzymes were strikingly elevated and GlcNAc-1-phosphotransferase activity in the patient's fibroblasts was 3% of normal. Sequence analysis of the patient's genomic DNA revealed a homozygous mutation of the last nucleotide of the 135-bp exon 7 of the phosphotransferase gene encoding the alpha/beta subunits, resulting in aberrant splicing and skipping of this exon. Remarkably, none of the skeletal and connective tissue anomalies characteristic of the disease were present. This case is the first example of mucolipidosis III presenting in an adult patient and further broadens the clinical spectrum of the disease.
Steet
Richard A
RA
Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
Hullin
Roger
R
Kudo
Mariko
M
Martinelli
Michele
M
Bosshard
Nils U
NU
Schaffner
Thomas
T
Kornfeld
Stuart
S
Steinmann
Beat
B
D017668:Age of Onset; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D009202:Cardiomyopathies / Q000150:complications*; D002402:Cathepsin D / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004699:Endocardium / Q000473:pathology / Q000648:ultrastructure; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009081:Mucolipidoses / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010766:Phosphorylation; D021122:Protein Subunits / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D021122:Protein Subunits; D004247:DNA; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase; D002402:Cathepsin D