Novel Mutations, Including a Large Deletion in the ARSB Gene, Causing Mucopolysaccharidosis Type VI

Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare autosomal recessive lysosomal storage disease, is caused by mutations in the N-acetylgalactosamine-4-sulfatase (arylsulfatase B, or ARSB) gene, resulting in a deficiency of ARSB activity. This study aimed to characterize the clinical and molecular features of four unrelated Thai patients with MPS VI. Two were products of consanguineous marriages.

The diagnosis was confirmed by biochemical and genetic tests. We performed mutation analysis by polymerase chain reaction-sequencing on the entire coding region of the ARSB gene. Array-based comparative genomic hybridization (aCGH) analysis combined with direct sequencing was also used to search for a deletion boundary.

The causative mutations were detected in all cases. Of four different mutations identified, three have never been previously described, which included two missense mutations (p.C155Y and p.R388T) and a deletion encompassing exons 2 and 3. Both missense mutations were absent in 110 unaffected ethnic-matched control chromosomes and an in-house database of 180 Thai exomes. The p.C155Y and p.R388T mutations were located in highly conserved residues. A CGH analysis combined with direct sequencing identified the breakpoints of a large 13,788 base pair deletion. It is the largest deletion of ARSB described to date in patients with MPS VI.

This study expanded the known mutational spectrum of ARSB; we identified three novel mutations; two of which are missense mutations and one that represents the largest deletion mutation identified to date in this gene.