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It is caused by variants in <jats:italic>ARSB<\/jats:italic>, which encodes the lysosomal arylsulfatase B (ARSB) enzyme, part of the degradation process of glycosaminoglycans in lysosomes. Over 220 variants have been reported so far, with a majority of missense variants. We hereby report two siblings of Bedouin origin with a diagnosis of MPS\u2010VI. Western blots in patient fibroblasts revealed total absence of ARSB protein production. Complete sequencing of the coding region of <jats:italic>ARSB<\/jats:italic> did not identify a candidate disease\u2010associated variant. However, deep sequencing of the noncoding region of <jats:italic>ARSB<\/jats:italic> by whole genome sequencing (WGS) revealed a c.1142+581A to G variant. The variant is located within intron 5 and fully segregated with the disease in the family. Determination of the genetic cause for these patients enabled targeted treatment by enzyme replacement therapy, along with appropriate genetic counseling and prenatal diagnosis for the family. These results highlight the advantage of WGS as a powerful tool, for improving the diagnostic rate of rare disease\u2010causing variants, and emphasize the importance of studying deep intronic sequence variation as a cause of monogenic disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.62453","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T11:04:23Z","timestamp":1629975863000},"page":"3804-3809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deep intronic variant in the <scp><i>ARSB<\/i><\/scp> gene as the genetic cause for Maroteaux\u2013Lamy syndrome (<scp>MPS VI<\/scp>)"],"prefix":"10.1002","volume":"185","author":[{"given":"Dina","family":"Marek\u2010Yagel","sequence":"first","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel\u2010Hashomer Israel"},{"name":"The Danek Gertner Institute of Human Genetics Sheba 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