GP58 Case report of hunter syndrome in mongolians

Background Mucopolysaccaridosis II (MPSII), Hunter syndrome, (OMIM# 309900) is a metabolic genetic disorder caused by deficiency of iduronate-2-sulfatase (IDS) enzyme necessary for step-wise degradation of glycosaminoglycan (GAG) in a cell. Point mutations and small deletions of exon 9 of IDS gene account for 50% of Hunter syndrome cases. Accumulation of GAG virtually in all cells causes MPS that is characterized by mental, growth progressive retardation, multiple system dysfunction and death usually occurs in first and second decade of life. MPS cases are diagnosed by only clinical symptoms in our country and detection of mutation, identification of defective enzymes, and carrier detection in the patient’s family is still missing. Purpose of this study was to diagnose MPS cases by molecular genetic analysis and detect carriers in case if mutation detected. Methods Iduronate-2 sulfatase enzyme activity was checked by tandem mass spectrometer. IDS gene mutation was analyzed in Hunter syndrome patients by direct sequencing. We used Multiplex Ligation-dependent Probe Amplification (MLPA) assay to detect×chromosome deletion in case if we could not amplify IDS gene. Results Totally we investigated four patients with MPS, and familial members of a case 3, who had a mutation in IDS gene. Proband-E showed clinical symptoms of Hurler syndrome, but Hunter syndrome was suspected by genealogical study, also enzyme deficiency of iduronate 2 sulfatase was used to differentiate his diagnosis. We could not amplify exons of IDS gene in this patient sample, suggesting that he might have a deletion in×chromosome, and also we could not identify deletion covering Xq28 using SALSA MPLA probemix P095–A3 Aneuploidy. Proband-A is from inbred parents, in whom we suggest to have autosomal recessive mutant alleles. Proband-T showed clinical symptoms of Hunter syndrome and pedigree analysis and enzyme deficiency analysis confirmed it. Mutation screening was done in exon 2, 3, 8 and 9 of IDS gene where most mutations reported in Hunter syndrome patients and a R468W mutation leading to a replacement of arginine 468 to tryptophan was detected in the patient. His mother carries mutant allele, as well as his three sisters. Proband I expresses clinical symptoms of Hunter syndrome and iduronate 2 sulfatase enzyme deficiency detected in blood samples which is confirmatory for Hunter syndrome. Conclusion This is a first genetic analysis of MPS cases in Mongolia. We detected R468W mutation in the patient with severe phenotype of Hunter syndrome. We also confirmed four female carriers in this family.