TY - JOUR
T1 - Null mutations and lethal congenital form of glycogen storage disease type IV
AU - Assereto, Stefania
AU - van Diggelen, Otto P.
AU - Diogo, Luisa
AU - Morava, Eva
AU - Cassandrini, Denise
AU - Carreira, Isabel
AU - de Boode, Willem Pieter
AU - Dilling, Jildau
AU - Garcia, Paula
AU - Henriques, Margarida
AU - Rebelo, Olinda
AU - ter Laak, Henk
AU - Minetti, Carlo
AU - Bruno, Claudio
PY - 2007/9/21
Y1 - 2007/9/21
N2 - 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.
AB - 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.
KW - GBE1 gene
KW - Glycogen branching enzyme deficiency
KW - Glycogen storage disease type IV
KW - Polyglucosan body
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U2 - 10.1016/j.bbrc.2007.07.074
DO - 10.1016/j.bbrc.2007.07.074
M3 - Article
C2 - 17662246
AN - SCOPUS:34547515164
SN - 0006-291X
VL - 361
SP - 445
EP - 450
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -