Identification and structure characterization of novel IDS variants causing mucopolysaccharidosis type II: A retrospective analysis of 30 Chinese children.

• This study analyzed IDS activity and gene mutations of 30 Chinese MPS II patients. • WES was performed on 30 subjects, and a total of 25 mutations were identified. • This study expands the spectrum of MPS II genotype. • This study provides new insights into the molecular mechanisms of MPS II. • This study contributes to future studies of genotype-phenotypic association. Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is a rare X-linked recessive genetic disease resulting from deficient activity of the iduronate-2-sulfatase(IDS) enzyme and the accumulation of glycosaminoglycans in almost all cells, tissues and organs, which makes viscera function impaired. This study retrospectively analyzed the clinical characteristics, leukocyte IDS activity and mutations in the IDS gene of 30 Chinese children with MPS II. Methods: Whole-exome sequencing (WES) was performed on samples of the 30 patients. Results: A total of 25 mutations were identified in the IDS genes including 16 previously reported and 9 novel mutations (6 frameshift: c.815-818dupAACG, c.1453dupA, c.1270-1271delGT, c.1484-1485insTA, c.854delA, c.12_13delCC; 3missense: c.325 T > G, c.140 T > C, c.248 T > G). The computer simulations of the protein structure analysis of the novel missense mutations showed these amino acid replacements (W109G tryptophan replaced by the glycine, L47P leucine replaced by the proline, V83G valine replaced by glycine) near the active site of IDS protein sulfatase domain and would cause a severe impairment of protein structure and function. Conclusions: Our study expands the spectrum of MPS II genotype, provides new insights into the molecular mechanisms of MPS II, and contributes to future studies of genotype-phenotypic associations to estimate prognosis and develop new treatment regimens. [ABSTRACT FROM AUTHOR]