Abstract
Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by mutations in alpha-L-iduronidase (IDUA) gene. IDUA contributes to the degradation of the glycosaminoglycans, including heparan sulphate and dermatan sulphate. Deficient activity of IDUA generates accumulation of glycosaminoglycans in lysosomes leading to MPS I. Here, we identified two boys with MPS I caused by a compound heterozygote of a reported \(\hbox {c.265C}>\hbox {T}\) (p.R89W) missense mutation in exon 2 and a novel \(\hbox {c.1633G}>\hbox {T}\) (p.E545*, 109) nonsense mutation in exon 11 of IDUA gene in a Chinese family. R89 is close to the active site and its replacement will affect the structure and function of IDUA. Besides, termination from E545 deletes one of the prominent domains and alters the spatial structure of IDUA. In conclusion, our study demonstrates a previously unrecognized mutation in IDUA gene and this report adds to the mutational spectrum observed.
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Acknowledgements
We would like to thank the patients and their family for their participation in this study. This work was supported by grants from the National Natural Science Foundation of China (no. 81770875, 81702156, 81572639), the Science and Technology Department of Sichuan Province (no. 2018SZ0142), Postdoctoral Science Foundation of China (no. 2017M61060) and the Sichuan University (no. 2018SCUH0093, 2017SCU12038).
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Corresponding Editor: H. A. Ranganath
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Li, Y., Tang, X., Meng, Y. et al. A novel compound mutation in alpha-L-iduronidase gene causes mucopolysaccharidosis type I. J Genet 98, 65 (2019). https://doi.org/10.1007/s12041-019-1113-2
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DOI: https://doi.org/10.1007/s12041-019-1113-2