1. Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene
- Author
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Rosella Tomanin, Nicole Miller, Litsa Karageorgos, Mitch Bailey, Alessandra Zanetti, John J. Hopwood, Hitoshi Sakuraba, Moeenaldeen Al-Sayed, Tomanin, Rosella, Karageorgos, Litsa, Zanetti, Alessandra, Al-Sayed, Moeenaldeen, Bailey, Mitch, Miller, Nicole, Sakuraba, Hitoshi, and Hopwood, John J
- Subjects
0301 basic medicine ,Arylsulfatase B ,medicine.medical_specialty ,Databases, Factual ,ASB ,databases ,N-Acetylgalactosamine-4-Sulfatase ,Genetic counseling ,MPS VI ,Mucopolysaccharidosis type VI ,Molecular Conformation ,Mutation, Missense ,Genomics ,Biology ,Mutation Updates ,03 medical and health sciences ,Gene Frequency ,Genetics ,medicine ,Humans ,Missense mutation ,Genetic Testing ,Allele ,Gene ,Societies, Medical ,Genetics (clinical) ,Genetics & Heredity ,variants ,Mutation Update ,Mucopolysaccharidosis VI ,Homozygote ,Genetic Variation ,arylsulfatase B ,Early Diagnosis ,030104 developmental biology ,Medical genetics ,ARSB ,lysosomal storage disorder - 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. Refereed/Peer-reviewed
- Published
- 2018