亨特结果调查得出的黏多醣症II患者基因型-表型结果

IF 3.7 2区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Molecular genetics and metabolism Pub Date : 2024-09-01 DOI:10.1016/j.ymgme.2024.108576
Joseph Muenzer , Hernan Amartino , Barbara K. Burton , Maurizio Scarpa , Anna Tylki-Szymańska , Jennifer Audi , Jaco Botha , Daniel Fertek , David Merberg , Madhusudan Natarajan , David A.H. Whiteman , Roberto Giugliani
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引用次数: 0

摘要

本研究利用亨特结果调查(HOS)登记数据,研究了粘多糖病II(MPS II)淀粉酸-2-硫酸酯酶基因(IDS)变异与表型特征(尤其是认知障碍)之间的关系。
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Genotype–phenotype findings in patients with mucopolysaccharidosis II from the Hunter Outcome Survey

Purpose

This study investigated the relationship between mucopolysaccharidosis II (MPS II) iduronate-2-sulfatase gene (IDS) variants and phenotypic characteristics, particularly cognitive impairment, using data from the Hunter Outcome Survey (HOS) registry.

Methods

HOS data for male patients (n = 650) aged ≥5 years at latest cognitive assessment with available genetic data were analyzed. Predefined genotype categories were used to classify IDS variants and report phenotypic characteristics by genotype.

Results

At their latest cognitive assessment, 411 (63.2%) of 650 patients had cognitive impairment. Missense variants were the most common MPS II genotype, with about equal frequency for patients with and patients without cognitive impairment. Complete deletions/large rearrangements were associated with cognitive impairment. Cognitive impairment and behavioral issues were most common, and height and weight abnormalities most apparent, in patients with large IDS structural changes. Broadly, missense variants NM-000202.8:c.998C>T p.(Ser333Leu), NM-000202.8:c.1402C>T p.(Arg468Trp), NM-000202.8:c.1403G>A p.(Arg468Gln) and NM-000202.8:c.262C>T p.(Arg88Cys), and splice site variant NM-000202.8:c.257C>T p.(Pro86Leu), were associated with cognitive impairment, and variants NM-000202.8:c.253G>A p.(Ala85Thr), NM-000202.8:c.187 A>G p.(Asn63Asp), NM-000202.8:c.1037C>T p.(Ala346Val), NM-000202.8:c.182C>T p.(Ser61Phe) and NM-000202.8:c.1122C>T were not.

Conclusion

This analysis contributes toward the understanding of MPS II genotype–phenotype relationships, confirming and expanding on existing findings in a large, geographically diverse population.

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来源期刊
Molecular genetics and metabolism
Molecular genetics and metabolism 生物-生化与分子生物学
CiteScore
5.90
自引率
7.90%
发文量
621
审稿时长
34 days
期刊介绍: Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.
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