In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 7, No. 9 ( 2019-09)
Abstract:
Mucopolysaccharidosis type I ( MPS I) is a rare, recessively inherited lysosomal storage disorder, characterized by progressive multi‐systemic disease. It is caused by a reduced or absent alpha‐l iduronidase ( IDUA ) enzyme activity secondary to biallelic loss‐of‐function variants in the IDUA . Over 200 causative variants in IDUA have been identified. Nevertheless, there is a fraction of MPS I patients with only a single mutated IDUA allele detectable. Methods As genetic testing of MPS I is usually based on sequencing methods, copy number variations ( CNV s) in IDUA can be missed and therefore presumably remain underdiagnosed. The aim of this study was the detection of CNV s using an IDUA ‐specific in house multiplex ligation‐dependent probe amplification ( MLPA ) assay. Results A total of five unrelated MPS I patient samples were re‐analyzed after only a single heterozygous IDUA mutation c.979G 〉 C (p.A327P), c.1469T 〉 C (p.L490P), c.1598C 〉 G (p.P533R), c.1205G 〉 A (p.W402X), c.973‐7C 〉 G (p.?) could be identified. We detected a novel splice site variant c.973‐7C 〉 G (p.?), as well as two novel CNV s, a large deletion of IDUA exon 14 and 3’ UTR c.(1828 + 1_1829‐1)_(*1963_?)del, and a large duplication extending from IDUA exon 2 to intron 12 c.(157 + 1_158‐1)_(1727 + 1_1728‐1)dup. Conclusion Together with the CNV s we previously identified, a total of four pathogenic IDUA CNV s have now been reported.
Type of Medium:
Online Resource
ISSN:
2324-9269
,
2324-9269
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2734884-2
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