Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy.
Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy.
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DOI：
10.1002/acn3.51612
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发表时间：
2022-08
影响因子：
5.3
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中科院分区：
文献类型：
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许多肌营养不良患者尽管进行了包括外显子组测序在内的临床诊断测试，但在基因上仍未得到诊断。有些可能含有以前未被检测到的结构变异(SVS)或神秘的剪接位点。我们招募了10个没有血缘关系的家庭：9个有肌肉营养不良，但缺乏完整的基因诊断，1个有无症状的DMD重复。纳米孔基因组长读测序在四个个体中发现了以前未检测到的致病变异：DMD中的一个SV，LAMA2中的一个SV，以及DMD中改变剪接的两个单核苷酸变体。在无症状个体中，DMD重复是同步的。纳米孔测序可能有助于简化肌营养不良症的基因诊断方法。
Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacked complete genetic diagnoses and one had an asymptomatic DMD duplication. Nanopore genomic long‐read sequencing identified previously undetected pathogenic variants in four individuals: an SV in DMD, an SV in LAMA2, and two single nucleotide variants in DMD that alter splicing. The DMD duplication in the asymptomatic individual was in tandem. Nanopore sequencing may help streamline genetic diagnostic approaches for muscular dystrophy.