Spectrum of GALNS mutations and haplotype study in Brazilian patients with Mucopolysaccharidosis type IVA

Mucopolysaccharidosis type IVA (MPS IVA or Morquio A syndrome) is an autosomal recessive disorder caused by mutations in the gene that encodes the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS), resulting in enzyme deficiency and non- degraded or partially degraded no degradation of the substrate keratan sulphate and chondroitin-6-sulfate. To date, 328 mutations have been identified in the GALNS gene. In this study, 25 different mutations were identified among 68 unrelated South-American patients with MPS IVA. Of the 25 alterations, 7 were novel, being predicted as probably pathogenic by bioinformatics analysis. The bioinformatics findings together with the lack of observation of these alterations in the existing databases, suggests that they are disease-causing mutations, and were correlated with biochemical findings. Additionally, we performed the analysis using intragenic polymorphisms to identify some association between any particular mutation and specific haplotype in Brazilian patients. We identified 14 different haplotypes, of these 10 were found only in controls. The mutation p.Ser341Arg was reported in the Brazilian patients and only in two patients from Sri Lanka. In our study, all patients with p.Ser341Arg mutation showed to be correlated with the same haplotype in all patients studied. Thus, we suggest the existence of a possible founder effect for this mutation.