IDUA mutational profile and genotype-phenotype relationships in UK patients with Mucopolysaccharidosis I

Abstract

Mucopolysaccharidosis Type 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 Mucopolysaccharidosis Type I for whom IDUA sequencing was performed, focussing 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 Mucopolysaccharidosis Type I is treated with haematopoietic 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 Mucopolysaccharidosis Type 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.

This article is protected by copyright. All rights reserved

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uDMust
via IFTTT