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

Area of Science:

• Genetics
• Biochemistry
• Molecular Biology

Background:

• Mucopolysaccharidosis type VI (MPS-VI), or Maroteaux-Lamy syndrome, is an inherited disorder caused by arylsulfatase B enzyme deficiency.
• This deficiency leads to glycosaminoglycan accumulation, causing tissue and organ enlargement.
• MPS-VI diagnosis requires clinical, biochemical, and molecular evaluation due to overlapping symptoms with other MPS disorders.

Purpose of the Study:

• To identify pathogenic variants in the ARSB gene in two unrelated Pakistani MPS-VI patients.
• To characterize the identified variants using in silico tools and ACMG guidelines.
• To contribute to the understanding of the MPS-VI mutation spectrum in the Pakistani population.

Main Methods:

• Clinical and biochemical assessments were performed for patient diagnosis.
• Direct DNA sequencing of all coding exons and intron-exon boundaries of the ARSB gene.
• Sanger sequencing, in silico variant pathogenicity prediction, and ACMG guideline classification.

Main Results:

• Two novel pathogenic variants in the ARSB gene were identified: a 2-bp deletion (c.511_512del) and a missense substitution (c.166G>A).
• In silico analysis predicted deleterious effects of these variants on arylsulfatase B protein function.
• The identified variants are associated with the MPS-VI phenotype in the studied patients.

Conclusions:

• The study expands the known mutation spectrum for Mucopolysaccharidosis type VI.
• The findings provide valuable information for genetic counseling and prenatal diagnosis for affected families.
• This represents a significant clinical and molecular genetic report of MPS-VI from Pakistan.