Molecular study of IDUA, IDS, GALNS and GLB1 gene mutations in the Azerbaijan population

For the first time in the Azerbaijan Republic, we carried out medical genetic consultation of affected children suspicious of lysosomal storage diseases, and particularly with mucopolysaccharidoses. Patients were from the cities of Baku, Gyandzhe and other areas of the Republic. Consultations were done by doctors: pediatrician and geneticist. As to clinical manifestations, 19 index patients and 54 members in their families: Hurler syndrome (1 patient), Hunter syndrome (5 patients), Morquio syndrome (13 patients). The NGS (Next Generation Sequencing) technique was used for molecular genetic diagnostics. In index patient suspicious with Hurler syndrome (MPSI) mutation of alpha-L-iduronidase (IDUA) (NP_000194,2: c.1882C>T, p.Arg628Ter) was identified in the homozygous state. Among patients with clinical manifestations of Hunter syndrome (MPSII) three mutations iduronate-2-sulfatase (IDS) gene: 1106C>G (p.Asp358Leu), c.322T>G (p.Asp358Leu) and c.1215del (p.Leu*34406Phefs) were identified in the hemizygous state. In patients with Morquio syndrome (MPSIVA) 9 mutations of the Nacetylgalactosamine-6-sulfatase (GALBS) gene and one mutation beta-galactosidase (GLB1) c.176G-A (p.Arg59His) Morquio syndrome (MPSIVB) were identified. Nine mutations are as follows: c.1144C>G (p.Leu382Val), c.1265A-G (p.Gln422Arg), c.463G-T (p.Gly155Cys), c.1018 G-T (p.Gly340Cys). c.157G>A (p.Gly53Arg), c.553C>T (p.Pro185Ser), c.443A>G (p.His148Arg), c.1283A>G (p.Gln428Arg), c.439T>A (p.Trp147Arg). When examining affected children's family members, 41 people with heterozygous carriage of the GALNS gene were identified: MPS 3, MPSII-12, MPSIVA-26, relatively. In one sibling of the index patient with Morquio syndrome (MPSIVA) c.463G-T (p.Gly155Cys) mutation was found in the homozygous state. Obtained experimental results allow doctors to direct patients to proper treatment as well as prophylactic activities with families including fetus prenatal diagnostics in the next pregnancies.