GLA GENE MUTATION IN PATIENTS WITH FABRY DISEASE

Abstract

Introduction: For the first time in the Lenkoran-Astara administrative area of Azerbaijan Republic, a genetic screening was conducted on patients with cardiomyopathies to identify Fabry metabolic disease. The screening involved the assessment of alpha-galactosidase enzyme activity and the globotriasylsphingosine level. This article aims to present the results of the screening and the subsequent molecular genetic analysis of the GLA gene in the identified patients. Materials and Methods. The genetic screening was based on applying fluorimetry and liquid chromatography methods. The Sanger sequencing technique was employed for direct sequencing of the GLA gene, enabling the detection of existing mutations. This technique was developed in CENTOGENE laboratories, Rostock, Germany. The initial tests were conducted at the Centogene laboratory in Rostock, Germany, followed by further testing at the GENOM clinical laboratory in Baku, Azerbaijan Republic. Ultrasonic and echocardiography studies were performed simultaneously with blood sampling at the central regional hospital. Results: 21 individuals out of 76 involved in the study had a deficiency in αgalactosidase enzyme activity and elevated levels of globotriasylsphingosine, indicative of Fabry disease. Among them, seven women exhibited X-linked inheritance as heterozygous, and three men were identified as homozygous. Molecular genetic analysis revealed two different mutations in the GLA gene: 801+3A>G and 137 A>G. To prevent Fabry disease, it is recommended to screen family members of affected individuals for α-galactosidase enzyme activity. Conclusion: This study represents the first genetic screening for Fabry disease conducted in the Azerbaijan Republic among patients with cardiological diseases. 21 individuals out of 76 examined patients were identified as having Fabry disease and carrying two different GLA gene mutations: c.801+3A>G and c.137A>G. The obtained genetic results will aid cardiologists to make accurate diagnosis and to select appropriate management for patients with cardiomyopathy, considering the presence of Fabry disease, as well as enabling prenatal foetus diagnostics during pregnancies in families at genetic risk.