Mutational analysis of ten Turkish patients with glycogen storage disease type III: identification of four novel mutations

Aim: AGL gene mutations are responsible for glycogen storage disease type Ill which is an autosomal recessive disorder. The distribution of these mutations shows a great variance in different populations. The aim of this study is to uncover the AGL gene mutation profile among Turkish patients and to contribute to the establishment of a link between these mutations and the clinical picture of the disease. Material and Method: A total of ten patients aged between two and eight years (mean age 1.7+1.1) who were diagnosed with glycogen storage disease type III by liver biopsy and enzymatic analysis from eight different families were included in this study. DNA was isolated from the peripheral blood samples of these patients and exons 6, 7, 9-18, 22, 24, 29-34 of the AGL gene were studied by DNA sequencing analysis. Results: Our study revealed two novel missense mutations p.G167V and p.Y173E two novel intronic single base substitutions c.1284-1G>A and c.2002-2A>T and a known single base substitution p.W1327X. Numerous intronic variants were also identified. As a result of the analysis of ten patients, SNP's rs3736296, IVS12-197T>G, rs2291637, rs2035961, rs2274570, rs6692695, rs296885 were found in 1, 6, 1, 1, 1, 1, and 2 of the 10 patients, respectively. Conclusions: According to the recent literature about the AGL gene which is constituted of a total of 35 coding exons, mutations have been reported frequently in exons 3, 4, 7, 16, 21, 25, 30 and 31. This study and previous studies reveal that the majority of the mutations identified in Turkish patients so far have been detected in exon 31 of the AGL gene. In addition, the distribution of AGL gene mutations in Turkish patients reflects the genetic heterogeneity in our population. (Turk Arch Ped 2012; 47:278-82)