title: 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: Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05, Institut Pasteur de Tunis, 1002, Tunis, Tunisia.
authors: Faten
authors: F
authors: Ben Rhouma
authors: Hatem
authors: H
authors: Azzouz
authors: François M
authors: FM
authors: Petit
authors: Mariem Ben
authors: MB
authors: Khelifa
authors: Amel Ben
authors: AB
authors: Chehida
authors: Fehmi
authors: F
authors: Nasrallah
authors: Frédéric
authors: F
authors: Parisot
authors: Khaled
authors: K
authors: Lasram
authors: Rym
authors: R
authors: Kefi
authors: Yosra
authors: Y
authors: Bouyacoub
authors: Lilia
authors: L
authors: Romdhane
authors: Christiane
authors: C
authors: Baussan
authors: Naziha
authors: N
authors: Kaabachi
authors: Marie-Françoise
authors: MF
authors: Ben Dridi
authors: Neji
authors: N
authors: Tebib
authors: Sonia
authors: S
authors: Abdelhak
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D023061:Gene Order; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D008297:Male; D017354:Point Mutation; D022821:RNA Splice Sites; D035781:Siblings; D014416:Tunisia
chemical_list: D006004:Glycogen Debranching Enzyme System; D022821:RNA Splice Sites
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