Wang Jia Dong James, Kimball Tamara N, Prapiadou Savvina, Low Xi Zhen, Vijayan Joy, Chin Hui-Lin, Tan Benjamin Yong-Qiang
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
Neurol Genet. 2025 Apr 17;11(3):e200261. doi: 10.1212/NXG.0000000000200261. eCollection 2025 Jun.
The aim of this study was to characterize the clinical, genetic, and radiologic presentation of a patient with gene duplication, including the duplication of the silencer region.
A patient who presented with muscle stiffness and constipation underwent comprehensive clinical and imaging evaluations, followed by next-generation whole-genome sequencing and optical genome mapping. In the subsequent year, the proband reported additional symptoms of muscle spasms, difficulty of relaxation of the anal sphincter, and stiffness in movements.
MRI of the brain demonstrated mild diffuse white matter hyperintensities bilaterally. Analysis of optical genome mapping data revealed a 275.54-kb tandem duplication at 5q23.2 [NC_000005.10:g.126637655_126913191dup] comprising 4 genes including the gene.
We identified a 69-year-old patient with an duplication who presented with a milder phenotype compared with typical -related autosomal-dominant leukodystrophy. The symptoms included dysautonomia and muscle stiffness. This distinct presentation is likely attributable to the duplication of the silencer region of , which may contribute to the milder symptoms observed.
本研究旨在描述一名基因重复患者的临床、遗传和影像学表现，包括沉默子区域的重复。
一名出现肌肉僵硬和便秘症状的患者接受了全面的临床和影像学评估，随后进行了下一代全基因组测序和光学基因组图谱分析。在接下来的一年里，先证者报告了肌肉痉挛、肛门括约肌松弛困难和运动僵硬等额外症状。
脑部MRI显示双侧轻度弥漫性白质高信号。光学基因组图谱数据分析显示，5q23.2处存在一个275.54 kb的串联重复[NC_000005.10:g.126637655_126913191dup]，包含4个基因，包括该基因。
我们鉴定出一名69岁的基因重复患者，与典型的相关常染色体显性白质营养不良相比，其表型较轻。症状包括自主神经功能障碍和肌肉僵硬。这种独特的表现可能归因于该基因沉默子区域的重复，这可能导致了观察到的较轻症状。
