Investigation of glucosidase alpha acid gene mutations in patients with pompe disease

Objective:This study aims to detect known or novel mutations in GAA using Sanger sequencing method in nine patients who were pre-diagnosed with Pompe disease, having proximal muscle weakness, exercise intolerance and respiratory difficulties. It is thought that the detection of mutation sites and diversity will be beneficial for the diagnosis, treatment and future studies of the disease. Method: A signed informed consent form were obtained from nine Pompe patients who applied to the Neurology outpatient clinic of Akdeniz University and agreed to participate to the study. Peripheral blood samples were taken from the patients and DNA isolation, primer design and mutation analysis were performed by using Sanger sequencing technology. Results: AST, ALT, LDH and total CK levels of the patients were evaluated. According to these results, a significant increase was observed in the liver-related enzymes AST, ALT and total CK levels. A total of five different heterozygous pathogenic mutations were detected in the patients. The c.-32-13T>G variant was detected in six of the patients in compound heterozygous state. In addition, the c.2662G>T variant was detected in six patients. Heterozygous c.1064T>C variant was found in one of the patients and heterozygous c.670C>T variants were detected in one patient. A novel pathogenic heterozygous c.2417_2418insG variant was detected in patient 8. No pathogenic variant was detected in one patient. Conclusion: The c.-32-13T>G variant with the highest prevalence worldwide for GAA was detected in six of nine patients. This suggests that the c.-32-13T>G variant may have a high prevalence in our country as well. As a result of the analysis, two variants of unknown clinical significance and extremely rare were detected. One of these two, c.1438G>A variant is estimated have a splicing effect and this supports the possiblity that it may be a pathogenic variant. Key words: Acid alpha glucosidase, autosomal recessive, Pompe disease, Sanger sequencing