Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype–phenotype 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 IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype–phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair 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–phenotype 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.

中文翻译：

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大量巴西亨特综合征患者的基因型-表型研究

粘多糖贮积症 II 型 (MPS II) 是一种由IDS基因中的致病变异引起的 X 连锁遗传疾病，导致溶酶体酶艾杜糖酸 2-硫酸酯酶缺乏，从而导致糖胺聚糖广泛储存，导致多种临床后果，并逐渐恶化。大多数情况下包括认知能力下降的表现。MPS II 具有广泛的等位基因和临床异质性以及复杂的基因型-表型相关性。我们评估了 1982 年至 2020 年诊断为 MPS II 的 501 名巴西患者的数据。我们对这些患者中的 280 名 (55.9%) 进行了基因分型，这些患者被分配到 206 个不同的家庭。70% 的患者存在点突变，其中错义变异最为常见。我们关联了IDS以表型（神经元病或非神经元病）鉴定的致病变异。除了两个同父异母兄弟外，家族成员之间的基因型-表型相关性没有不一致，来自不同家族的具有相同单碱基对替换变异的 MPS II 患者之间也没有不一致。在 82.0% 的病例中，母亲是携带者。这项对巴西 MPS II 病例分子谱的综合研究揭示了基因型-表型相关性，有助于更好地了解疾病和预测其临床病程，从而为受影响的患者提供更精细的遗传咨询。家庭。