Department of Child and Adolescent Neurology, LR18SP04, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia.
Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, Hassan II University, Casablanca, Morocco.
Mol Genet Genomic Med. 2019 Sep;7(9):e914. doi: 10.1002/mgg3.914. Epub 2019 Jul 31.
RNA polymerase III (Pol III)-related leukodystrophies are a group of autosomal recessive neurodegenerative disorders caused by mutations in POLR3A and POLR3B. Recently a recessive mutation in POLR1C causative of Pol III-related leukodystrophies was identified.
We report the case of a Tunisian girl of 14 years of age who was referred to our department for evaluation of progressive ataxia that began at the age of 5. Genetic diagnosis was performed by NGS and Sanger analysis. In silico predictions were performed using SIFT, PolyPhen-2, and Mutation Taster.
Neurological examination showed cerebellar and tetrapyramidal syndrome, mixed movement disorders with generalized dystonia and severe myoclonus leading to death at 25 years. Brain MRI scans showed diffuse hypomyelination associated with cerebellar atrophy. It also showed bilateral T2 hypointensity of the ventrolateral thalamus, part of the posterior limb of the internal capsule, the substantia nigra and the subthalamic nucleus. Next generation sequencing leukodystrophy panel including POLR3A and POLR3B was negative. Sanger sequencing of the coding regions of POLR1C revealed a novel homozygous mutation.
The clinical and imaging findings of patients with POLR1C hypomyelinating leukodystrophy are reviewed. Interestingly, severe myoclonic dystonia and T2 hypointensity of the substantia nigra and the subthalamic nucleus are not reported yet and could be helpful for the diagnosis of POLR1C hypomyelinating leukodystrophy.
RNA 聚合酶 III（Pol III）相关脑白质营养不良是一组由 POLR3A 和 POLR3B 基因突变引起的常染色体隐性神经退行性疾病。最近，发现 POLR1C 的隐性突变可导致 Pol III 相关脑白质营养不良。
我们报告了一名 14 岁的突尼斯女孩的病例，她因 5 岁时开始的进行性共济失调而被转至我们科进行评估。通过 NGS 和 Sanger 分析进行遗传诊断。使用 SIFT、PolyPhen-2 和 Mutation Taster 进行了种系预测。
神经系统检查显示小脑和锥体外系综合征，伴有全身性肌张力障碍和严重肌阵挛的混合运动障碍，导致 25 岁死亡。脑 MRI 扫描显示弥漫性脑白质发育不良伴小脑萎缩。还显示双侧腹外侧丘脑、内囊后肢、黑质和丘脑底核的 T2 低信号。POLR3A 和 POLR3B 在内的下一代测序脑白质营养不良小组为阴性。POLR1C 编码区的 Sanger 测序显示了一种新的纯合突变。
我们回顾了 POLR1C 脑白质发育不良性脑白质营养不良患者的临床和影像学发现。有趣的是，严重肌阵挛性肌张力障碍和黑质和丘脑底核的 T2 低信号尚未报道，这可能有助于 POLR1C 脑白质发育不良性脑白质营养不良的诊断。
