Characterization of an IDS pathogenic variant in a family with mucopolysaccharidosis type Ⅱ / 中华内分泌代谢杂志
Chinese Journal of Endocrinology and Metabolism
; (12): 345-352, 2023.
Article
en Zh
| WPRIM
| ID: wpr-994332
Biblioteca responsable:
WPRO
ABSTRACT
Objective:
To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS) c.323A>C.Methods:
A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected.Results:
The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity.Conclusion:
The variant IDS c.323A>C p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.
Texto completo:
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Base de datos:
WPRIM
Idioma:
Zh
Revista:
Chinese Journal of Endocrinology and Metabolism
Año:
2023
Tipo del documento:
Article