Egyptian glycogen storage disease type III - identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId.
BACKGROUND
Glycogen storage disease type III (GSD III) is caused by mutations in AGL which encodes for a single protein with two enzyme activities: oligo-1, 4-1, 4-glucantransferase (transferase) and amylo-1, 6-glucosidase. Activity of both enzymes is lost in most patients with GSD III, but in the very rare subtype IIId, transferase activity is deficient. Since the spectrum of AGL mutations is dependent on the ethnic group, we investigated the clinical and molecular characteristics in Egyptian patients with GSD III.


METHODS
Clinical features were examined in five Egyptian patients. AGL was sequenced and AGL haplotypes were determined.


RESULTS
Six novel AGL mutations were identified: a large deletion (c.3481-3588+1417del1525 bp), two insertions (c.1389insG and c.2368insA), two small deletions (c.2223-2224delGT and c.4041delT), and a missense mutation (p.L620P). p.L620P was found in a patient with IIId. Each mutation was located on a different AGL haplotype.


CONCLUSIONS
Our results suggest that there is allelic and phenotypic heterogeneity of GSD III in Egypt. This is the second description of a large deletion in AGL. p.L620P is the second mutation found in GSD IIId.
Endo
Yoriko
Y
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Fateen
Ekram
E
El Shabrawy
Mortada
M
Aoyama
Yoshiko
Y
Ebara
Tetsu
T
Murase
Toshio
T
Podskarbi
Teodor
T
Shin
Yoon S
YS
Okubo
Minoru
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004534:Egypt; D006004:Glycogen Debranching Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017384:Sequence Deletion; D014166:Transferases / Q000378:metabolism
D006004:Glycogen Debranching Enzyme System; D014166:Transferases