IDS gene

The IDS gene (IDS stands for: iduronate 2-sulfatase) is a protein-coding gene localized on Xq28. Alternative splicing leads to several transcript variants, at least one of which codes for a preprotein that is proteolytically processed. An important paralog of this gene is ARSD.

The IDS gene encodes a member of the sulfatase family of proteins. The encoded preprotein is proteolytically processed to produce two polypeptide chains. The encoded sulfatase is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate.

Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Blaschko-linear hyperpigmentation associated with mucopolysaccharidosis type II (Sofronova V et al. 2023) and Mongolian spots have been described

Mucopolysaccharidosis type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene.

In a larger (n=130) Chinese cohort with MPS II, the following symptoms were found (Zhang Z et al.2023):

• claw-like hands
• coarse facial features
• birthmarks (Mongolian spot)
• developmental delays
• Inguinal or umbilical hernias.
• Cardiac manifestations:
  • Mitral/tricuspid valve regurgitation (71.9 %)
  • Aortic/pulmonary valve regurgitation (36.8 %).

To date, 43 different IDS-pathogenic gene variants have been identified. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55).

1. Sofronova V et al. (2023) A Case of Mucopolysaccharidosis II Caused by a Novel Variant with Skin Linear Hyperpigmented Streaks along Blaschko's Lines. Int J Mol Sci 24:5647.
2. Zhang Z et al.(2023) Phenotypic and genetic characteristics of 130 patients with mucopolysaccharidosis type II: A single-center retrospective study in China. Front Genet 14:1103620.