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A splicing mutation in the α/β GlcNAc‐1‐phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy
Author(s) -
Steet Richard A.,
Hullin Roger,
Kudo Mariko,
Martinelli Michele,
Bosshard Nils U.,
Schaffner Thomas,
Kornfeld Stuart,
Steinmann Beat
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30498
Subject(s) - mucolipidosis , exon , phosphotransferase , mutation , rna splicing , biology , cardiomyopathy , genetics , glycogen storage disease , gene , medicine , endocrinology , pathology , disease , biochemistry , enzyme , heart failure , rna
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 α/β 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. © 2005 Wiley‐Liss, Inc.