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Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene
- Source :
- Human Mutation
- Publication Year :
- 2018
- Publisher :
- Hindawi Limited, 2018.
-
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
- 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
Subjects
Details
- ISSN :
- 10597794
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Human Mutation
- Accession number :
- edsair.doi.dedup.....19ce30ba334cd66969ceb3ba41ee1350