Null mutations and lethal congenital form of glycogen storage disease type IV.
until further notice
SourceBiochemical and Biophysical Research Communications, 361, 2, (2007), pp. 445-450
Article / Letter to editor
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Biochemical and Biophysical Research Communications
SubjectDCN 1: Perception and Action; IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 4: Glycostation disorders; IGMD 8: Mitochondrial medicine; UMCN 3.1: Neuromuscular development and genetic disorders; UMCN 5.1: Genetic defects of metabolism
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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