1. Molecular and biochemical characterization of a novel intronic single point mutation in a Tunisian family with glycogen storage disease type III
- Author
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Khaled Lasram, Fehmi Nasrallah, Yosra Bouyacoub, Sonia Abdelhak, Marie-Françoise Ben Dridi, Frédéric Parisot, Mariem Ben Khelifa, Neji Tebib, Rym Kefi, François Petit, Hatem Azzouz, Amel Ben Chehida, Faten Ben Rhouma, Lilia Romdhane, Christiane Baussan, Naziha Kaabachi, Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), Unité des Maladies Neurologiques de l'Enfant, Faculte de Medecine de Tunis, Département de Pédiatrie, Unité des maladies métaboliques héréditaires, Hôpital La Rabta [Tunis], Laboratoire de Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biochimie, Université de Carthage - University of Carthage, Hôpital Bicêtre, and The study was supported by the Tunisian Ministry of Public Health and the Ministry of Higher education and Scientific Research.
- 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 - 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.
- Published
- 2013