Exploring Molecular and Phenotypic Characteristics of NAGLU Arg234Gly and Asp312Asn Variants.

IF 0.9 4区医学 Q4 GENETICS & HEREDITY

Molecular Syndromology Pub Date : 2025-08-01 Epub Date: 2024-11-06 DOI:10.1159/000542367

Hande Kaymakcalan Celebiler, Tanyeri Barak, Devendra K Rai, Ilyas Kaya, Seda Erbilgin, Merve Cikili Uytun, Didem Oztop, Hakan Gumus, Huseyin Per, Serdar Ceylaner, Icten Bozkurt, Maria I Kontaridis, Kaya Bilguvar, Nilay Akhun, Ayse Kilincaslan, Ahmet Okay Caglayan, E Zeynep Erson-Omay, Murat Gunel, A Gulhan Ercan-Sencicek

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引用次数: 0

Abstract

Introduction: Mucopolysaccharidosis type IIIB is an autosomal recessive lysosomal disorder caused by variants in the α-n-acetylglucosaminidase (NAGLU) gene. It is a progressive neurodegenerative disorder with no treatment. Previous enzyme therapies have been unsuccessful. It is important to understand the mechanism of the disease to be able to find new treatments.

Methods: We did whole-exome sequencing and standard Sanger sequencing on 7 cases of four consanguineous families diagnosed with autism spectrum disorder.

Results: We identified two recurrent damaging biallelic Asp312Asn and p.Arg234Gly variants in the NAGLU gene. Structure modeling of these variants suggested that each variant affects the stability of the enzyme and results in a loss of activity. All affected individuals' enzymatic assay in leukocytes clearly showed that α-n-acetylglucosaminidase was completely inactive. Our patients underwent magnetic resonance imaging (MRI), revealing normal findings in two of them despite progressive clinical neurodegenerative symptoms. To our knowledge, these cases represent the second and third instances of normal MRI findings documented in the literature.

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探讨NAGLU Arg234Gly和Asp312Asn变异的分子和表型特征。

IIIB型粘多糖病是由α-n-乙酰氨基葡萄糖酶（NAGLU）基因变异引起的常染色体隐性溶酶体疾病。这是一种无法治疗的进行性神经退行性疾病。以前的酶疗法都不成功。了解这种疾病的机制对于找到新的治疗方法是很重要的。方法：对诊断为自闭症谱系障碍的4个近亲家庭的7例患者进行全外显子组测序和标准Sanger测序。结果：我们在NAGLU基因中发现了两个复发性损伤双等位基因Asp312Asn和p.a g234gly变异。这些变异的结构建模表明，每个变异都会影响酶的稳定性并导致活性丧失。所有受影响个体的白细胞酶分析均清楚地表明α-n-乙酰氨基葡萄糖酶完全失活。我们的病人接受了核磁共振成像（MRI），尽管他们的临床神经退行性症状进展，但结果显示正常。据我们所知，这些病例代表了文献中记录的第二和第三例正常MRI结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.