Mucopolysaccharidoses types I and IIIA: Diagnosis and identification of novel polymorphisms associated with common mutations in Moroccan patients

Background

Mucopolysaccharidoses types I and IIIA are lysosomal storage diseases caused by mutations in the IDUA and SGSH genes, leading to deficiencies in α-L-iduronidase and heparan sulfamidase, respectively. These progressive, autosomal recessive disorders require early diagnosis.

Purpose

The study targeted and investigated the p.Pro533Arg mutation, known to cause mucopolysaccharidosis type I, and the p.Arg377Cys mutation, associated with mucopolysaccharidosis IIIA, in newly recruited Moroccan families. In parallel, variants/polymorphisms associated with these mutations were searched for.

Methods

Researchers employed RFLP assays for the p.Pro533Arg and p.Arg377Cys mutations and genomic PCR sequencing for variant detection. PolyPhen-2, MutPred2, SIFT, and MutationTaster were used to assess the pathogenicity of these variants, helping to evaluate their potential impact on disease.

Results

The p.Pro533Arg mutation was found in newly recruited families with Hurler syndrome, consistent with previous findings. Similarly, the p.Arg377Cys mutation was present in a newly recruited family with Sanfilippo A syndrome. DNA sequencing revealed five SNPs four in the IDUA gene and one in the SGSH gene with three IDUA SNPs and one SGSH SNP being novel.

Conclusion

The p.Pro533Arg and p.Arg377Cys mutations are common among Moroccan patients with MPS I and MPS IIIA, respectively. The ability to detect these mutations using restriction endonucleases allows for molecular diagnosis in affected families. Five polymorphisms were identified among them four are novel.