Null mutations and lethal congenital form of glycogen storage disease type IV
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- 作者：Stefania Assereto ; Otto P. van Diggelen ; Luisa Diogo ; Eva Morava ; Denise Cass ; rini ; Isabel Carreira ; Willem-Pieter de Boode ; Jildau Dilling ; Paula Garcia ; Margarida Henriques ; Olinda Rebelo ; Henk ter
- 关键词：Glycogen storage disease type IV ; Glycogen branching enzyme deficiency ; GBE1 gene ; Polyglucosan body
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 出版时间：21 September 2007
- 年：2007
- 卷：361
- 期：2
- 页码：445-450
- 全文大小：876 K
文摘
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.