ABSTRACT Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease caused by mutations in the IDUA gene, resulting in decreased activity of the lysosomal enzyme α‐ l ‐iduronidase (IDUA) and consequent accumulation of glycosaminoglycans in the lysosomes. There are more than 300 disease‐causing variants reported in the IDUA gene, and the mutational profile varies considerably worldwide. In this study, we performed molecular analysis on 119 MPS I patients, representing the largest Brazilian cohort studied so far. Forty‐seven different mutations were identified in our sample, and 13 of them are newly described: c. 48delG, c. 78delC, c. 159‐23₁59‐1del23, p. Gln125Ter, p. Trp175Ter, c. 590‐6ins4G, c. 763delC, c. 973‐1G>A, p. Asp349Glu, p. Asn350Lys, p. Lys384Asn, c. 1403‐12₁403‐4del9, and p. Lys546Ter. In silico analysis of novel variants suggests they are possibly pathogenic, supporting previous biochemical and clinical diagnoses. Among recurrent mutations, p. Trp402Ter and p. Pro533Arg are the most frequent in Brazil, found in 42. 4% and 16% of the alleles, respectively. These results reveal the great allelic heterogeneity of IDUA variants in Brazilian patients. Unraveling the genetic profile of MPS I patients may improve the diagnosis and management of this rare disease.
Cruz et al. (Thu,) studied this question.