Rosdi Siti Nornazihah Mohd, Omar Suzuanhafizan, Ghazali Mazira Mohamad, Ghani Ab Rahman Izaini, Yusoff Abdul Aziz Mohamed
Abdul Aziz Mohamed Yusoff, Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia,
Croat Med J. 2025 Feb 28;66(1):56-61. doi: 10.3325/cmj.2025.66.56.
Chiari malformation type 1 (CM 1) is a rare and complex neurological condition. This congenital condition affects the lower posterior fossa, where the brain connects to the spinal cord. Although the exact cause of CM 1 remains unclear, genetic predisposition plays a considerable role in structural defects of the cerebellum. Here, we report on a 15-year-old female patient with CM 1 who exhibited both nuclear and mitochondrial genetic variants, a combination that has not been previously described. We identified a silent mutation in exon 2 (c. 556 G>A, p. Lys185=) of PAX1 and a DKK1 variant in intron 3 (548-3 t>C) in the nuclear DNA. We also screened the D-loop region of mitochondrial DNA as it exhibits a higher susceptibility to mutations than other mitochondrial DNA regions. Several hotspot variants were revealed, including those in positions 303-309 and 16519 (t>C), as well as some variants that had not been documented in MITOMAP. Our findings highlight the potential role of genetic alterations in D-loop in CM 1.
1型Chiari畸形（CM 1）是一种罕见且复杂的神经系统疾病。这种先天性疾病会影响脑与脊髓相连的后颅窝下部。虽然CM 1的确切病因尚不清楚，但遗传易感性在小脑结构缺陷中起着相当重要的作用。在此，我们报告一例15岁患有CM 1的女性患者，该患者同时表现出核基因和线粒体基因变异，这种组合此前尚未见报道。我们在核DNA中鉴定出PAX1外显子2（c. 556 G>A，p. Lys185=）的一个沉默突变以及内含子3（548 - 3 t>C）中的一个DKK1变异。我们还筛查了线粒体DNA的D环区域，因为该区域比其他线粒体DNA区域更容易发生突变。发现了几个热点变异，包括303 - 309位和16519位（t>C）的变异，以及一些在MITOMAP中未记录的变异。我们的研究结果突出了D环基因改变在CM 1中的潜在作用。
