Institute for Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Neuropediatrics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Clin Epigenetics. 2024 Aug 2;16(1):101. doi: 10.1186/s13148-024-01711-0.
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.
适应性纳米孔测序作为一种诊断印记障碍的方法，通过外显子 6 和 7 的基因内重复分析，在一个具有相对轻度的 Angelman 样综合征的患者中发现了 UBE3A（NM_000462.5）中的基因内重复。在一体化纳米孔测序分析中，已知母源等位基因缺失的 SNURF:TSS-DMR 的 DNA 低甲基化和 UBE3A 的点突变可以排除作为疾病驱动因素。相比之下，可以明确界定串联重复的断点和方向。家系的分离分析表明，该重复是从母系祖父那里新发生的。我们的研究表明，一体化纳米孔测序方法在 Angelman 综合征和其他印记障碍的诊断中具有优势。
