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Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate

Journal of Human Genetics (2025)Cite this article

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Abstract

Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans that play indispensable roles in multiple physiological processes, including cell proliferation, cell adhesion, development, neuronal guidance, and cartilage formation. Depletion of CS/DS caused by biosynthetic enzyme loss of function impairs these processes and results in embryonic lethality. However, some individuals with mutant enzymes survive and exhibit severe phenotypes. These rare hereditary diseases have been discovered and characterized in recent decades because of marked advances in next-generation sequencing technology. In this review, CS/DS-related inherited diseases caused by aberrations in both CS/DS backbone synthesis, as well as their sulfation and/or epimerization, are comprehensively summarized and their pathogenesis discussed.

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Fig. 1: CS/DS biosynthesis.
Fig. 2: Non-enzymatic roles of FAM20C in fine-tuning of CS sulfation balance and Raine syndrome etiology.
Fig. 3: Schematic of collagen fibrils and decorin-proteoglycan with CS/DS side chains.

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Funding

This work was supported in part by a Grant-in-Aid for Scientific Research (C) 23K06142 (to SM), 24K09372 (to TM), and 24K09805 (to SY), and Scientific Research (B) 24K02183 (to HK) from the Japan Society for the Promotion of Science, Japan.

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  1. These authors contributed equally: Tadahisa Mikami, Shuji Mizumoto.

Authors and Affiliations

  1. Laboratory of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan

    Tadahisa Mikami & Hiroshi Kitagawa

  2. Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan

    Shuji Mizumoto & Shuhei Yamada

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  1. Tadahisa Mikami
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  2. Shuji Mizumoto
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  3. Hiroshi Kitagawa
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  4. Shuhei Yamada
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Correspondence to Hiroshi Kitagawa or Shuhei Yamada.

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Mikami, T., Mizumoto, S., Kitagawa, H. et al. Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate. J Hum Genet (2025). https://doi.org/10.1038/s10038-025-01396-0

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