■面肩肱肌营养不良症(FSHD)是一种常见的肌营养不良症,主要影响骨骼肌。FSHD1占所有FSHD病例的95%,可以根据染色体4q35上D4Z4重复序列的致病性收缩进行诊断。由于D4Z4区域的大尺寸和重复性质,FSHD1的遗传诊断具有挑战性。我们评估了光学基因组作图(OGM)在FSHD1基因诊断中的临床适用性。
■我们纳入了25名临床确诊或疑似/可能的FSHD患者及其家属。外周血中的超高分子量DNA被标记,染色,并使用单分子OGM平台(BionanoGenomicsSaphyr系统)进行成像。使用制造商的专用管道分析D4Z4重复大小和单倍型信息。我们还比较了Southern印迹分析和OGM之间的工作流程和测试时间。
■我们从临床证实的FSHD患者的10个样本中获得了一致的OGM和Southern印迹结果。在Southern印迹分析和OGM之间,D4Z4重复大小在1个单位内不同。在9名临床怀疑或可能的FSHD患者中,6例患者经OGM证实有致病性收缩.在我们的队列中,1例FSHD1患者成功诊断为OGM。此外,与Southern印迹分析相比,OGM的工作流程更简单,耗时更少。
■OGM能够准确可靠地检测D4Z4-重复序列阵列的致病性收缩,是FSHD1遗传诊断的有价值的工具。
UNASSIGNED: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1.
UNASSIGNED: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer\'s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM.
UNASSIGNED: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM. In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM. Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis.
UNASSIGNED: OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.