Molecular analysis and novel variation identification of Chinese pedigrees with mucopolysaccharidosis using targeted next-generation sequencing

Background: Mucopolysaccharidosis (MPS) refers to a group of lysosomal storage disorders for which seven types and 11 subtypes are currently recognized. Targeted next-generation sequencing (NGS) offers an important method of disease typing, diagnosis, prenatal diagnosis, and treatment.

Methods: Gene variations in 48 Chinese MPS patients were evaluated using NGS, and the pathogenicity of the DNA alterations was evaluated using PolyPhen2, SIFT, and Mutation Taster. The effect of amino acid substitution on protein structure was also assessed.

Results: Four pedigrees with MPS I (8.3%), 28 with MPS II (58.3%), two with MPS IIIA (4.2%), two with MPS IIIB (4.2%), six with MPS IVA (12.5%), one with MPS IVB (2.1%), and five with MPS VI (10.4%) were identified. Of the 69 variations identified, 11 were novel variants (three in IDUA, five in IDS, and three in GALNS), all of which were predicted to be disease-causing except for one, and were associated with impaired protein structure and function.

Conclusions: Targeted NGS technology is effective for the gene-based testing of MPS disorders, which show high allelic heterogeneity. MPS II was the predominant form in Chinese. Our study expands the existing variation spectrum of MPS, which is important for disease management and genetic counseling.