1. Functional characterization of arylsulfatase B mutations in Indian patients with Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI)
- Author
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Ashwin Dalal, Prajnya Ranganath, Anusha Uttarilli, and Divya Pasumarthi
- Subjects
0301 basic medicine ,Arylsulfatase B ,Male ,Adolescent ,N-Acetylgalactosamine-4-Sulfatase ,Mucopolysaccharidosis type VI ,DNA Mutational Analysis ,India ,Biology ,Gene mutation ,Dermatan sulfate ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,Chlorocebus aethiops ,Genetics ,medicine ,Animals ,Humans ,Child ,Gene ,Mucopolysaccharidosis VI ,Base Sequence ,Mutagenesis ,Infant ,General Medicine ,medicine.disease ,Molecular biology ,Recombinant Proteins ,Maroteaux–Lamy syndrome ,030104 developmental biology ,Phenotype ,chemistry ,Child, Preschool ,COS Cells ,Mutation ,Mutation testing ,Female ,Mutant Proteins - Abstract
MPS VI is an autosomal recessive disorder which occurs due to the deficiency of N-acetyl galactosamine-4-sulfatase (Arylsulfatase B - ARSB) involved in catabolism of dermatan sulfate resulting from disease-causing variations in the ARSB gene. Human Gene Mutation Database (HGMD) search revealed 200 different mutations in ARSB worldwide. In the present study we carried out molecular and functional analyses to characterize the mutations reported by us in Indian population. Mutation analysis of 19 MPS VI patients revealed presence of a total of 15 different mutations of which twelve were novel [p.Asp53Asn (c.157G>A; p.D53N), p.Leu98Arg (c.293T>G; p.L98R), p.Tyr103Serfs*9 (c.306_312delCTACCAG+146del; p.Y103Sfs*9), p.Phe166Leufs*18 (c.496delT; p.F166Lfs*18), p.Ile220Serfs*5 (c.659_660delTA; p.I220Sfs*5), p.Ile350Phe (c.1048A>T; p.I350F), p.Trp353* (c.1059G>A; p.W353*), p.His393Arg (c.1178A>G; p.H393R), p.Ser403Tyrfs* (c.1208delC; p.S403Yfs*), p.Pro445Leu (c.1334C>T; p.P445L), p.Trp450Leu (c.1349G>T; p.W450L) and p.Trp450Cys (c.1350G>C; p.W450C)] and three were known mutations [p.Asp54Asn (c.160G>A; p.D54N), p.Ala237Asp (c.710C>A; p.A237D) and p.Ser320Arg (c.960C>G; p.S320R)]. Functional characterization using site-directed mutagenesis followed by cell transfection assays, immunoblot, reverse transcriptase PCR and immunofluorescence studies for the putative pathogenic variants detected in our MPS VI patient cohort helped us to confirm the pathogenic potential of the variants in ARSB.
- Published
- 2016