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Molecular and biochemical characterization of a novel intronic single point mutation in a Tunisian family with glycogen storage disease type III
- Source :
- Molecular Biology Reports, Molecular Biology Reports, Springer Verlag, 2013, 40 (7), pp.4197-202. ⟨10.1007/s11033-013-2500-z⟩
- Publication Year :
- 2013
-
Abstract
- International audience; Genetic deficiency of the glycogen debranching enzyme causes glycogen storage disease type III, an autosomal recessive inherited disorder. The gene encoding this enzyme is designated as AGL gene. The disease is characterized by fasting hypoglycemia, hepatomegaly, growth retardation, progressive myopathy and cardiomyopathy. In the present study, we present clinical features and molecular characterization of two consanguineous Tunisian siblings suffering from Glycogen storage disease type III. The full coding exons of the AGL gene and their corresponding exon-intron boundaries were amplified for the patients and their parents. Gene sequencing identified a novel single point mutation at the conserved polypyrimidine tract of intron 21 in a homozygous state (IVS21-8A>G). This variant cosegregated with the disease and was absent in 102 control chromosomes. In silico analysis using online resources showed a decreased score of the acceptor splice site of intron 21. RT-PCR analysis of the AGL splicing pattern revealed a 7 bp sequence insertion between exon 21 and exon 22 due to the creation of a new 3' splice site. The predicted mutant enzyme was truncated by the loss of 637 carboxyl-terminal amino acids as a result of premature termination. This novel mutation is the first mutation identified in the region of Bizerte and the tenth AGL mutation identified in Tunisia. Screening for this mutation can improve the genetic counseling and prenatal diagnosis of GSD III.
- Subjects :
- Male
Novel mutation
Tunisia
AGL gene
[SDV]Life Sciences [q-bio]
DNA Mutational Analysis
Biology
Glycogen storage disease type III
Aberrant splicing
Glycogen debranching enzyme
03 medical and health sciences
Exon
Consanguinity
Glycogen Storage Disease Type III
Glycogenosis type III
Gene Order
Genetics
medicine
Humans
Point Mutation
RT-PCR Tunisian patients
Molecular Biology
Gene
030304 developmental biology
0303 health sciences
Point mutation
Siblings
030305 genetics & heredity
Intron
Infant, Newborn
Infant
Glycogen Debranching Enzyme System
General Medicine
medicine.disease
Molecular biology
Introns
3. Good health
Polypyrimidine tract
Mutation (genetic algorithm)
Female
RNA Splice Sites
Subjects
Details
- ISSN :
- 15734978 and 03014851
- Volume :
- 40
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecular biology reports
- Accession number :
- edsair.doi.dedup.....fd30d407a4aff63b74c66a6564688dcc