Report of Mucopolysaccharidosis Type VI Disorder in Pakistani Patients Presenting Two Novel ARSB Variants.

Mucopolysaccharidosis type VI (MPS-VI, Maroteaux-Lamy syndrome) is an inherited progressive disorder caused by the deficiency of the arylsulfatase B enzyme encoded by the ARSB gene. The deficient enzyme activity results in the accumulation of glycosaminoglycans in lysosomes with consequent enlargement of multiple tissues and organs. Due to overlapping clinical symptoms of MPS-VI with other MPS disorders, diagnosis is based on cumulative evaluation of clinical, biochemical, and molecular investigations. The current study recruited two unrelated Pakistani patients suffering from MPS-VI. The diagnosis of the patients was based on clinical assessments and biochemical parameters. We performed direct DNA sequencing of the ARSB gene to screen for pathogenic variants in the patients and their families. All coding exons and intron-exon boundaries were PCR-amplified and subjected to Sanger sequencing. In silico tools were used to predict the pathogenicity of the variants, which were then classified according to the ACMG guidelines. Molecular screening of the patients identified two novel variants: a 2-bp deletion NM_000046.5:c.511_512del and a missense substitution NM_000046.5:c.166G>A. In silico evaluation supported the deleterious effects of the identified variants on the protein function, leading to the MPS-VI phenotype. The study has its significance in expanding the mutation spectrum and may help the affected families in genetic counseling and prenatal diagnosis. To our knowledge, this is the second clinical and molecular genetic report of MPS-VI from Pakistan.