LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia.
Department of Neuroradiology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia.
Mol Genet Genomic Med. 2024 Oct;12(10):e70007. doi: 10.1002/mgg3.70007.
POLIII-related leukodystrophies are a group of recently recognized hereditary white matter diseases with a similar clinical and radiological phenotype. No Tunisian studies have been published about POLIII-related leukodystrophy due to POLR3A variants. The aim of this study was to contribute to the clinical, radiological, and genetic characterization of POLR3A-related leukodystrophy in a Tunisian cohort.
We report six cases of genetically confirmed POLR3A-related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.
All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15 months and 6 years. The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients. Molecular analysis identified the same bi-allelic NM_007055.4:c.2011T>C; p.(Trp671Arg) variant in the POLR3A gene in all patients.
We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian POLR3A patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.
POLIII 相关脑白质病是一组新近认识的遗传性脑白质疾病，具有相似的临床和影像学表型。由于 POLR3A 变异，突尼斯尚未发表关于 POLIII 相关脑白质病的研究。本研究旨在对突尼斯队列中 POLR3A 相关脑白质病的临床、放射学和遗传学特征进行研究。
我们报告了六例经基因证实的 POLR3A 相关脑白质病，这些患者来自六个不相关的突尼斯家庭，并对以前发表的儿科病例进行了回顾。
所有患者均为近亲结婚所生，来自突尼斯北部或中部。发病年龄在 15 个月至 6 岁之间。所有患者的临床表型相似，均有小脑性共济失调、震颤和眼球震颤等主要特征。脑影像学显示所有患者均有弥漫性脑白质发育不良，其中 3 例有进行性小脑萎缩。分子分析发现所有患者均携带 POLR3A 基因的相同双等位基因 NM_007055.4:c.2011T>C；p.(Trp671Arg) 变异。
鉴于 6 个不相关个体具有相似的临床表型，我们推测该变异存在一个共同的起源。鉴于突尼斯 POLR3A 患者的遗传明显同质性，应直接针对反复出现的变异进行研究。这将有助于在索引患者中进行诊断和遗传咨询。
