利用光学基因组图谱技术诊断杜氏肌营养不良1例报告

Diagnosis of a child with Duchenne muscular dystrophy using optical genome mapping

目的 初步探讨光学基因组图谱技术(OGM)在杜氏肌营养不良(DMD)中的诊断价值。方法 对1例疑似DMD的患儿进行OGM分析,以期发现致病的分子基础。结果 1例男性患儿,7月龄时发现肌酸激酶显著升高,临床疑诊DMD。经多重连接依赖性探针扩增分析(MLPA)和全外显子组测序检测均未发现致病性基因变异。21月龄独走不稳,易摔跤,查体发现双侧腓肠肌肥大、肌力低下。2岁时通过OGM识别出DMD基因内一个长约711kb的臂内倒位,涉及该基因44~55号区段的12个外显子,实现了该患儿的分子诊断。结论 OGM技术能够成功识别出DMD基因的倒位突变,有望成为该病的补充诊断手段。

Objective To explore the application of optical genome mapping(OGM)in the diagnosis of Duchenne muscular dystrophy(DMD).Methods An OGM analysis was performed in a child with suspected DMD with a view to discovering the molecular basis of the pathogenesis.Results A male child with significantly elevated creatine kinase at 7 months of age was clinically suspected of having DMD.No pathogenic gene variants were detected by multiplex ligationdependent probe amplification analysis(MLPA)and exome sequencing.At 1 year and 9 months,the child was unstable and prone to falls,and bilateral gastrocnemius muscle hypertrophy and muscle weakness were detected on physical examination.At the age of 2 years,an intra-arm inversion of about 711 kb involving 12 exons of the 44-55 region of the gene was identified by OGM,which enabled the molecular diagnosis of this child.Conclusions OGM technology can successfully detect the reverse mutation of the DMD gene,and is thus poised to become a supplementary diagnostic tool for this disease.