Abstract |
Glycogen branching enzyme deficiency ( glycogen storage disease type IV, GSD-IV) is a rare autosomal recessive disorder of the glycogen synthesis with high mortality. Two female newborns showed severe hypotonia at birth and both died of cardiorespiratory failure, at 4 and 12 weeks, respectively. In both patients, muscle biopsies showed deposits of PAS-positive diastase-resistant material and biochemical analysis in cultured fibroblasts showed markedly reduced glycogen branching enzyme activity. Direct sequencing of GBE1 gene revealed that patient 1 was homozygous for a novel c.691+5 g>c in intron 5 (IVS5+5 g>c). RT-PCR analysis of GBE1 transcripts from fibroblasts cDNA showed that this mutation produce aberrant splicing. Patient 2 was homozygous for a novel c.1643G>A mutation leading to a stop at codon 548 in exon 13 (p.W548X). These data underscore that in GSD-IV a severe phenotype correlates with null mutations, and indicate that RNA analysis is necessary to characterize functional consequences of intronic mutations.
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Authors | Stefania Assereto, Otto P van Diggelen, Luisa Diogo, Eva Morava, Denise Cassandrini, Isabel Carreira, Willem-Pieter de Boode, Jildau Dilling, Paula Garcia, Margarida Henriques, Olinda Rebelo, Henk ter Laak, Carlo Minetti, Claudio Bruno |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 361
Issue 2
Pg. 445-50
(Sep 21 2007)
ISSN: 0006-291X [Print] United States |
PMID | 17662246
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- DNA, Complementary
- 1,4-alpha-Glucan Branching Enzyme
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Topics |
- 1,4-alpha-Glucan Branching Enzyme
(chemistry, genetics)
- Amino Acid Sequence
- Base Sequence
- Biopsy
- Blotting, Western
- DNA Mutational Analysis
- DNA, Complementary
- Exons
(genetics)
- Fatal Outcome
- Female
- Fibroblasts
(enzymology)
- Glycogen Storage Disease Type IV
(genetics)
- Humans
- Infant, Newborn
- Introns
(genetics)
- Molecular Sequence Data
- Muscle, Skeletal
(enzymology, pathology)
- Mutation
(genetics)
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