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The gene responsible for MPS IIIC is<jats:italic>HGSNAT<\/jats:italic>, which encodes an enzyme that catalyses the acetylation of the terminal glucosamine residues of heparan sulfate. So far, few studies have focused on the genetic landscape of MPS IIIC in China, where IIIA and IIIB were the major subtypes. In this study, we utilized whole\u2010exome sequencing (WES) to identify novel compound heterozygous variants in the<jats:italic>HGSNAT<\/jats:italic>gene from a Chinese patient with typical MPS IIIC symptoms: c.743G&gt;A; p.Gly248Glu and c.1030C&gt;T; p.Arg344Cys. We performed in silico analysis and experimental validation, which confirmed the deleterious pathogenic nature of both variants, as evidenced by the loss of HGSNAT activity and failure of lysosomal localization. To the best of our knowledge, the MPS IIIC is first confirmed by clinical, biochemical and molecular genetic findings in China. Our study thus expands the spectrum of MPS IIIC pathogenic variants, which is of importance to dissect the pathogenesis and to carry out clinical diagnosis of MPS IIIC. Moreover, this study helps to depict the natural history of Chinese MPS IIIC populations.<\/jats:p>","DOI":"10.1111\/jcmm.18307","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T09:05:00Z","timestamp":1712999100000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification and characterization of novel genetic variants in the first Chinese family of mucopolysaccharidosis<scp>IIIC<\/scp>(Sanfilippo C syndrome)"],"prefix":"10.1111","volume":"28","author":[{"given":"Hongjun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Xiangya Hospital Central South University Changsha China"},{"name":"Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital Central South University Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South 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