通过自适应纳米孔测序发现一例由 UBE3A 基因内重复引起的安杰尔曼综合征病例

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2024-08-02 DOI:10.1186/s13148-024-01711-0

Laura Holthöfer, Stefan Diederich, Verena Haug, Lioba Lehmann, Charlotte Hewel, Norbert W Paul, Susann Schweiger, Susanne Gerber, Matthias Linke

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引用次数: 0

摘要

自适应纳米孔测序作为印记紊乱和表征分析的一种诊断方法，在一名相对轻微的安杰尔曼样综合征患者身上发现了 UBE3A (NM_000462.5) 第 6 和第 7 外显子的基因内重复。在一体化纳米孔测序分析中，SNURF:TSS-DMR 的 DNA 低甲基化、母系等位基因的已知缺失以及 UBE3A 中的点突变均可被排除在疾病驱动因素之外。与此相反，串联重复的断点和方向可以明确界定。该家族的分离分析表明，该重复序列来自外祖父。我们的研究显示了一体化纳米孔测序方法在诊断安杰曼综合征和其他印记疾病方面的优势。

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A case of an Angelman-syndrome caused by an intragenic duplication of UBE3A uncovered by adaptive nanopore sequencing.

Adaptive nanopore sequencing as a diagnostic method for imprinting disorders and episignature analysis revealed an intragenic duplication of Exon 6 and 7 in UBE3A (NM_000462.5) in a patient with relatively mild Angelman-like syndrome. In an all-in-one nanopore sequencing analysis DNA hypomethylation of the SNURF:TSS-DMR, known contributing deletions on the maternal allele and point mutations in UBE3A could be ruled out as disease drivers. In contrast, breakpoints and orientation of the tandem duplication could clearly be defined. Segregation analysis in the family showed that the duplication derived de novo in the maternal grandfather. Our study shows the benefits of an all-in-one nanopore sequencing approach for the diagnostics of Angelman syndrome and other imprinting disorders.

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.