Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene. Issue 12 (17th September 2018)

• Record Type: Journal Article
• Authors: Tomanin, Rosella; Karageorgos, Litsa; Zanetti, Alessandra; Al‐Sayed, Moeenaldeen; Bailey, Mitch; Miller, Nicole; Sakuraba, Hitoshi; Hopwood, John J.
• Is Part Of: Human mutation. Volume 39:Issue 12(2018)
• Page Start: 1788
• Page End: 1802
• Publication Date: 2018-09-17
• Subjects: ARSB -- arylsulfatase B -- ASB -- databases -- lysosomal storage disorder -- MPS VI -- variants; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23613
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: Maroteaux–Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage disorder caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection of ARSB pathogenic variants can independently confirm diagnosis and render genetic counseling possible. In this review, we collect and summarize 908 alleles (201 distinct variants, including 3 polymorphisms previously considered as disease‐causing variants) from 478 individuals diagnosed with MPS VI, identified from literature and public databases. Each variant is further analyzed for clinical classification according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results highlight the heterogeneity of ARSB alleles, with most unique variants (59.5%) identified as missense and 31.7% of unique alleles appearing once. Only 18% of distinct variants were previously recorded in public databases with supporting evidence and clinical significance. ACMG recommends publishing clinical and biochemical data that accurately characterize pathogenicity of new variants in association with reporting specific alleles. Variants analyzed were sent to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/ ), and MPS VI locus‐specific database (http://mps6-database.org ) where they will be available. High clinical suspicion coupled with diagnostic testing for deficient ASB activity and timely submission and classification of ARSB variants with biochemical and clinical data in public databases is essential for timely diagnosis of MPS VI. Abstract : Maroteaux–Lamy (MPS VI) is caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B enzyme. This analysis sought to collect and summarize 908 alleles (201 distinct variants) from 478 individuals with Maroteaux–Lamy. Variants were further analyzed for clinical classification according to ACMG guidelines, which were sent to ClinVar and MPS VI locus‐specific database. ARSB variants with biochemical and clinical data in public databases is essential for timely diagnosis of MPS VI.