Background and Purpose: Mucopolysaccharidosis 1 (MPS1) is an autosomal recessive disorder of a lysosomal enzyme called alpha-l-iduronidase caused by mutations in the IDUA gene. This enzyme is responsible for the degradation of the mucopolysaccharides, heparan sulfate, and dermatan sulfate. Based on clinical features and enzyme deficiency, MPS1 is divided into three subtypes, including a severe subtype (Hurler syndrome), an intermediate subtype (Hurler-Scheie syndrome), and an attenuated subtype (Scheie syndrome). The objective of this study was to characterize the mutation profiles of 17 Iranian patients with MPS1 and characterize the clinical features associated with their genotypes. Materials and Methods: Polymerase chain reaction-based sequencing of the IDUA gene was carried out for 10 patients with clinical diagnoses of MPS1 and 50 healthy controls. To estimate the impact of newly identified variants on the structure and function of the encoded alpha-l-iduronidase, in silico analyses was performed. Results: Eight genetic variations were detected, including five missense mutations (p.M1L, p.G51D, p.G134V, p.S157P, p.D301E), two nonsense mutations (p.W402* and p.Y343*), and one deletion (p.GFLNYY197-202), among which p.G134V, p.S157P, p.D301E, and p.GFLNYY197-202 were novel variations that had not been previously reported. Conclusion: After combining the results of the two previous IDUA gene studies performed on Iranian MPS1 patients and the results obtained from the current study, it is inferred that despite the presence of a number of previously known mutations, about half of the detected variations were unique in Iranian patients.
Keywords: PCR-sequencing; alpha-l-iduronidase; lysosomal storage disorder; mucopolysaccharidosis type 1.