A novel compound heterozygote mutation in the ARSB gene in a patient with Maroteaux-Lamy syndrome and its Insilico evaluation

Abstract Background Maroteaux-Lamy syndrome (Mucopolysaccharidosis VI (MPS VI)) is a rare autosomal recessive disorder resulted from a deficiency in N-acetylgalactosamine 4-sulfatase (Arylsulfatase B, ASB). The enzyme deficiency leads to accumulation of Dermatan sulfate (DS) in connective tissue which causes phenotypes related to MPS VI. Over 145 disease-causing mutations in the ARSB gene have been identified and reported in the Human Gene Mutation Database ( http://www.hgmd.cf.ac.uk/ac/index.php April 2018). This study aimed to characterize molecular and clinical features of a MPS VI patient who was the result of a consanguineous marriage and perform Insilico analysis of the mutated protein. Methods In this study, we scanned the ARSB gene of an Afghan patient lived in Iran and previously confirmed as MPS VI by clinical examinations and enzymatic assay. We performed DNA extraction, polymerase chain reaction and direct sequencing on the entire coding region and exon-intron junctions. The structure of mutated enzyme was evaluated by Insilico analysis. Results Two missense mutations were found in exon six (c.1178A > G (p.H393R) c.1210C > G (p.P404A) which predicted to be disease causing. Conclusion These findings implicate the compound heterozygote mutation in ARSB gene and could be important for prenatal diagnosis. This is the first study and the first compound heterozygote that we report in this region of Asia.

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