Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes

Pâmella Borges, Gabriela Pasqualim, Roberto Giugliani, Filippo Vairo, Ursula Matte

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: In this study, the prevalence of different types of mucopolysaccharidoses (MPS) was estimated based on data from the exome aggregation consortium (ExAC) and the genome aggregation database (gnomAD). The population-based allele frequencies were used to identify potential disease-causing variants on each gene related to MPS I to IX (except MPS II). Methods: We evaluated the canonical transcripts and excluded homozygous, intronic, 3′, and 5′ UTR variants. Frameshift and in-frame insertions and deletions were evaluated using the SIFT Indel tool. Splice variants were evaluated using SpliceAI and Human Splice Finder 3.0 (HSF). Loss-of-function single nucleotide variants in coding regions were classified as potentially pathogenic, while synonymous variants outside the exon–intron boundaries were deemed non-pathogenic. Missense variants were evaluated by five in silico prediction tools, and only those predicted to be damaging by at least three different algorithms were considered disease-causing. Results: The combined frequencies of selected variants (ranged from 127 in GNS to 259 in IDUA) were used to calculate prevalence based on Hardy–Weinberg's equilibrium. The maximum estimated prevalence ranged from 0.46 per 100,000 for MPSIIID to 7.1 per 100,000 for MPS I. Overall, the estimated prevalence of all types of MPS was higher than what has been published in the literature. This difference may be due to misdiagnoses and/or underdiagnoses, especially of the attenuated forms of MPS. However, overestimation of the number of disease-causing variants by in silico predictors cannot be ruled out. Even so, the disease prevalences are similar to those reported in diagnosis-based prevalence studies. Conclusion: We report on an approach to estimate the prevalence of different types of MPS based on publicly available population-based genomic data, which may help health systems to be better prepared to deal with these conditions and provide support to initiatives on diagnosis and management of MPS.

Original languageEnglish (US)
Article number324
JournalOrphanet Journal of Rare Diseases
Issue number1
StatePublished - Dec 2020


  • Estimated prevalence
  • Exome aggregation consortium (ExAC)
  • Genome aggregation database (gnomAD)
  • In silico analysis
  • Mucopolysaccharidoses (MPS)

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


Dive into the research topics of 'Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes'. Together they form a unique fingerprint.

Cite this