Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, Cairo, Egypt.
Ann Clin Transl Neurol. 2022 Dec;9(12):2025-2035. doi: 10.1002/acn3.51679. Epub 2022 Oct 18.
Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.
先前已有研究表明，铁硫簇支架蛋白（NFU1）的双等位基因突变与多种线粒体功能障碍综合征 1（MMDS1）相关，该疾病的特征为早发且迅速致命的脑白质病。我们报道了 10 个独立家系的 19 名受影响个体，他们携带极罕见的 NFU1 错义双等位基因突变，与一系列早发性纯合至复杂遗传性痉挛性截瘫（HSP）表型相关，该表型的生存时间较长（19 名中有 16 名），而在疾病的另一个极端则表现为神经发育迟缓伴严重的肌张力低下（19 名中有 3 名）。在该队列中，发热性疾病后常有可逆或不可逆的神经功能恶化，神经影像学上始终存在白质异常。该研究表明，MMDS1 和 HSP 可能是 NFU1 相关表型连续体的两个极端。
