Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China.
Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
Ann Clin Transl Neurol. 2024 Nov;11(11):3019-3024. doi: 10.1002/acn3.52195. Epub 2024 Sep 28.
FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element.
FARS2 相关遗传性痉挛性截瘫，迟发性痉挛性截瘫 77 型，是一种罕见的神经退行性疾病。在此，我们报道了一个常染色体隐性痉挛性截瘫家系中的 2 位受累同胞，他们携带 FARS2 的假纯合错义变异和 Alu 介导的外显子 5 缺失。这 2 位患者逐渐出现步态改变和双下肢无力。在我们的文献复习中，痉挛性截瘫 77 型在临床表现上具有高度异质性。本研究扩展了由 FARS2 复合杂合突变引起的 SPG77 的发病机制范围，并提供了强有力的证据表明，FARS2 中的缺失是由 Alu 元件介导的重组事件引起的。
