title: Molecular characterization of Egyptian patients with glycogen storage disease type IIIa.
abstract: Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and muscles and caused by a deficiency in the glycogen debranching enzyme. The spectrum of AGL mutations in GSD IIIa patients depends on ethnic group-prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe islands, because of the founder effect, whereas heterogeneous mutations are responsible for the pathogenesis in Japanese patients. To shed light on molecular characteristics in Egypt, where high rate of consanguinity and large family size increase the frequency of recessive genetic diseases, we have examined three unrelated patients from the same area in Egypt. We identified three different individual AGL mutations; of these, two are novel deletions [4-bp deletion (750-753delAGAC) and 1-bp deletion (2673delT)] and one the nonsense mutation (W1327X) previously reported. All are predicted to lead to premature termination, which completely abolishes enzyme activity. Three consanguineous patients are homozygotes for their individual mutations. Haplotype analysis of mutant AGL alleles showed that each mutation was located on a different haplotype. Our results indicate the allelic heterogeneity of the AGL mutation in Egypt. This is the first report of AGL mutations in the Egyptian population.
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Biochemical Genetics Department, National Research Centre, Cairo, Egypt.
authors.forename: Ekram
authors.initials: E
authors.lastname: Fateen
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Horinishi
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Ebara
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
authors.affiliation: Department of Pediatrics, University of Muenchen, Muenchen, Germany.
authors.forename: Yoon S
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. QFG00550@nifty.ne.jp.|Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan. QFG00550@nifty.ne.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
mesh_terms: D000483:Alleles; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000201:enzymology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D006004:Glycogen Debranching Enzyme System