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IDUA mutational profile and genotype–phenotype relationships in UK patients with Mucopolysaccharidosis Type I
Author(s) -
Ghosh Arunabha,
Mercer Jean,
Mackin Sabrina,
Yue Wyatt W,
Church Heather,
Beesley Clare E,
Broomfield Alex,
Jones Simon A,
Tylee Karen
Publication year - 2017
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23301
Subject(s) - mucopolysaccharidosis type i , biology , genotype , context (archaeology) , phenotype , mucopolysaccharidosis , disease , cohort , genetics , transplantation , hematopoietic stem cell transplantation , genotype phenotype distinction , immunology , stem cell , medicine , enzyme replacement therapy , gene , paleontology , biochemistry
Mucopolysaccharidosis Type I (MPS I) is a lysosomal storage disorder with varying degrees of phenotypic severity caused by mutations in IDUA . Over 200 disease‐causing variants in IDUA have been reported. We describe the profile of disease‐causing variants in 291 individuals with MPS I for whom IDUA sequencing was performed, focusing on the UK subset of the cohort. A total of 63 variants were identified, of which 20 were novel, and the functional significance of the novel variants is explored. The severe form of MPS I is treated with hematopoietic stem cell transplantation, known to have improved outcomes with earlier age at treatment. Developing genotype–phenotype relationships would therefore have considerable clinical utility, especially in the light of the development of newborn screening programs for MPS I. Associations between genotype and phenotype are examined in this cohort, particularly in the context of the profile of variants identified in UK individuals. Relevant associations can be made for the majority of UK individuals based on the presence of nonsense or truncating variants as well as other associations described in this report.