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MPS II has wide allelic and clinical heterogeneity and a complex genotype\u2013phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the <jats:italic>IDS<\/jats:italic> pathogenic variants identified with the phenotype (neuronophatic or non\u2010neuronopathic). Except for two half\u2010brothers, there was no discordance in the genotype\u2013phenotype correlation among family members, nor among MPS II patients from different families with the same single base\u2010pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype\u2013phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.<\/jats:p>","DOI":"10.1002\/ajmg.c.31915","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T18:38:43Z","timestamp":1620499123000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genotype\u2013phenotype studies in a large cohort of Brazilian patients with Hunter syndrome"],"prefix":"10.1002","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7506-993X","authenticated-orcid":false,"given":"Juliana Alves","family":"Josahkian","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Hospital Universit\u00e1rio de Santa Maria 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