Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

Wiley Online Library published: 13 June 2019 https://doi.org/10.1111/cge.13583

Lorne A. Clarke, Roberto Giugliani, Nathalie Guffon, Simon A. Jones, Hillary A. Keenan, Maria V. Munoz‐Rojas, Torayuki Okuyama, David Viskochil, Chester B. Whitley, Frits A. Wijburg, Joseph Muenzer

The genotype/phenotype relationships in this extensive series of 538 MPS I patients confirms and extends earlier observations that a large portion of severe MPS I patients (67.6%) have two IDUA variants that would be predictive of null alleles. Consequently, these data show that homozygosity or compound heterozygosity for two severe variants always leads to severe disease. In this series of Registry patients, none of the 158 attenuated patients had genotypes where both variants would predict severe disruption of transcription or translation; however, 95.6% (151/158) of attenuated patients had at least one missense variant with the remainder having at least one splice site, intronic or small in‐frame deletion variant.

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