Molecular and biochemical characterization of a novel intronic single point mutation in a Tunisian family with glycogen storage disease type III.

Abstract

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.

• Authors: Faten Ben Rhouma, Hatem Azzouz, François M Petit, Mariem Ben Khelifa, Amel Ben Chehida, Fehmi Nasrallah, Frédéric Parisot, Khaled Lasram, Rym Kefi, Yosra Bouyacoub, Lilia Romdhane, Christiane Baussan, Naziha Kaabachi, Marie-Françoise Ben Dridi, Neji Tebib, Sonia Abdelhak
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 40 Issue 7 Pg. 4197-202 (Jul 2013) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 23649758 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycogen Debranching Enzyme System
• RNA Splice Sites

Topics

• Consanguinity
• DNA Mutational Analysis
• Female
• Gene Order
• Glycogen Debranching Enzyme System (genetics)
• Glycogen Storage Disease Type III (genetics, metabolism)
• Humans
• Infant
• Infant, Newborn
• Introns
• Male
• Point Mutation
• RNA Splice Sites
• Siblings
• Tunisia