HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Null mutations and lethal congenital form of glycogen storage disease type IV.

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.
AuthorsStefania 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
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 361 Issue 2 Pg. 445-50 (Sep 21 2007) ISSN: 0006-291X [Print] United States
PMID17662246 (Publication Type: Case Reports, Journal Article)
Chemical References
  • DNA, Complementary
  • 1,4-alpha-Glucan Branching Enzyme
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: