Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Mov Disord. 2023 Sep;38(9):1750-1755. doi: 10.1002/mds.29522. Epub 2023 Jul 2.
To diagnose the molecular cause of hereditary spastic paraplegia (HSP) observed in a four-generation family with autosomal dominant inheritance.
Multiplex ligation-dependent probe amplification (MLPA), whole-exome sequencing (WES), and RNA sequencing (RNA-seq) of peripheral blood leukocytes were performed. Reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were used to characterize target regions of SPAST.
A 121-bp AluYb9 insertion with a 30-bp poly-A tail flanked by 15-bp direct repeats on both sides was identified in the edge of intron 16 in SPAST that segregated with the disease phenotype.
We identified an intronic AluYb9 insertion inducing splicing alteration in SPAST causing pure HSP phenotype that was not detected by routine WES analysis. Our findings suggest RNA-seq is a recommended implementation for undiagnosed cases by first-line diagnostic approaches. © 2023 International Parkinson and Movement Disorder Society.
对一个四代常染色体显性遗传的家族中观察到的遗传性痉挛性截瘫（HSP）进行分子诊断。
对外周血白细胞进行多重连接依赖性探针扩增（MLPA）、全外显子组测序（WES）和 RNA 测序（RNA-seq）。采用逆转录聚合酶链反应（RT-PCR）和 Sanger 测序对 SPAST 的靶区域进行特征分析。
在 SPAST 的内含子 16 边缘发现了一个 121-bp 的 AluYb9 插入，其带有 30-bp 的 poly-A 尾巴，两侧为 15-bp 的直接重复，与疾病表型分离。
我们鉴定出一个内含子 AluYb9 插入，导致 SPAST 剪接改变，引起纯 HSP 表型，这在常规 WES 分析中无法检测到。我们的研究结果表明，对于一线诊断方法无法诊断的病例，RNA-seq 是一种推荐的实施方法。© 2023 国际帕金森病和运动障碍协会。
