Identification and characterization of novel genetic variants in the first Chinese family of mucopolysaccharidosis IIIC (Sanfilippo C syndrome)

In this study, we utilized whole-exome sequencing (WES) to identify novel compound heterozygous variants in the HGSNAT gene from a Chinese patient with typical MPS IIIC symptoms: c.743G>A; p.Gly248Glu and c.1030C>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.PMID:38613342 | PMC:PMC11015392 | DOI:10.1111/jcmm.18307

Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Hongjun Zhao Lijing Wang Mengfei Zhang Huakun Wang Sizhe Zhang Junjiao Wu Yu Tang Source Type: research