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Publications

Journal Article Epublish

PubMed: 42378005 DOI: 10.1590/1678-4685-GMB-2025-0174

Variant profile of Brazilian patients with Sanfilippo syndrome type B.

Genet Mol Biol 49(2):e20250174

Authors: Alice Brinckmann Oliveira Netto, Ana Carolina Brusius-Facchin, Kristiane Michelin-Tirelli, Fernanda Medeiros SebastiĆ£o, Franciele Barbosa Trapp, Roberto Giugliani, Guilherme Baldo

Affiliations

  • Universidade Federal do Rio Grande do Sul, Programa de PĆ³s-GraduaĆ§Ć£o em GenĆ©tica e Biologia Molecular, Porto Alegre, RS, Brazil.
  • Instituto de GenĆ©tica para Todos, Porto Alegre, RS, Brazil.
  • Hospital de ClĆ­nicas de Porto Alegre, ServiƧo de GenĆ©tica MĆ©dica, Porto Alegre, RS, Brazil.
  • Hospital de ClĆ­nicas de Porto Alegre, ServiƧo de GenĆ©tica MĆ©dica, Rede MPS Brasil, Porto Alegre, RS, Brazil.
  • DASA GenĆ“mica, SĆ£o Paulo, SP, Brazil.
  • Instituto Nacional de GenĆ©tica MĆ©dica Populacional, Porto Alegre, RS, Brazil.
  • Universidade Federal do Rio Grande do Sul, Departamento de Fisiologia, Porto Alegre, RS, Brazil.

Abstract

Mucopolysaccharidosis type IIIB (MPS IIIB, or Sanfilippo syndrome type B) is a lysosomal storage disorder caused by variants in the NAGLU gene, leading to heparan sulfate accumulation. This study analyzed 27 MPS IIIB Brazilian patients diagnosed via the MPS Brazil Network (2014-2022). Diagnosis involved biochemical tests [NAGLU enzyme activity, urinary glycosaminoglycans (GAG)], showing expected low activity of the enzyme and high concentration of GAGs. Molecular analysis of the NAGLU gene by Sanger sequencing or Targeted Next-Generation Sequencing confirmed the diagnosis. Forty-nine variants were found across patient alleles, comprising twenty-two different variants. Two variants were described for the first time: p.Gly79Arg and p.Leu598Pro (both missense). In silico tools predicted the novel variants as damaging/deleterious. The study identified 90.7% of the expected mutant alleles, observing variant heterogeneity and a higher frequency of missense variants. This characterization enhances understanding of the Brazilian MPS IIIB genetic landscape and is instrumental to the design of diagnostic and screening strategies.

MeSH

Genes, Mucopolysaccharidosis Iii, Enzymes, Alleles