Maternal mosaicism for IDUA deletion clarifies recurrence risk in MPS I

Catherine Breen; Jean Mercer; Simon A Jones; Amir Jahic; Lesley Heptinstall; Karen Tylee; William G Newman; Christian Beetz

doi:10.1038/hgv.2016.31

Maternal mosaicism for IDUA deletion clarifies recurrence risk in MPS I

Hum Genome Var. 2016 Oct 6:3:16031. doi: 10.1038/hgv.2016.31. eCollection 2016.

Authors

Catherine Breen¹, Jean Mercer¹, Simon A Jones¹, Amir Jahic², Lesley Heptinstall¹, Karen Tylee¹, William G Newman¹, Christian Beetz²

Affiliations

¹ Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester Foundation Trust , Manchester, UK.
² Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital , Jena, Germany.

Abstract

Mucopolysaccharidosis I (MPS I) is a rare autosomal recessive multisystem lysosomal storage disorder. It is caused by biallelic loss-of-function variants in IDUA, encoding alpha-l iduronidase. Here, we describe an individual affected by MPS I due to a paternally inherited deletion of IDUA exons 1 and 2, c.(?_-88)_(299+1_300-1)del and a whole-gene deletion of IDUA (?_-88?)_(*136?)del secondary to maternal somatic mosaicism. We define a previously unreported mutational mechanism for this disorder.