title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Steet
authors.forename: Roger
authors.initials: R
authors.lastname: Hullin
authors.forename: Mariko
authors.initials: M
authors.lastname: Kudo
authors.forename: Michele
authors.initials: M
authors.lastname: Martinelli
authors.forename: Nils U
authors.initials: NU
authors.lastname: Bosshard
authors.forename: Thomas
authors.initials: T
authors.lastname: Schaffner
authors.forename: Stuart
authors.initials: S
authors.lastname: Kornfeld
authors.forename: Beat
authors.initials: B
authors.lastname: Steinmann
mesh_terms: 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
chemical_list: D021122:Protein Subunits; D004247:DNA; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase; D002402:Cathepsin D