Sánchez-Iglesias Sofía, Fernández-Pombo Antía, Cobelo-Gómez Silvia, Hermida-Ameijeiras Álvaro, Alarcón-Martínez Helena, Domingo-Jiménez Rosario, Ruíz Riquelme Alejandro Iván, Requena Jesús R, Araújo-Vilar David
UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
J Clin Med. 2021 Apr 1;10(7):1435. doi: 10.3390/jcm10071435.
Seipin, encoded by the gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia's encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.
由 基因编码的丝蛋白（seipin）是一种在人类中主要在中枢神经系统表达的蛋白质。独特的是， 中的某些变异可导致2型全身性先天性脂肪营养不良、上运动神经元和/或下运动神经元疾病或进行性脑病，儿童期预后较差。后者即西莉亚脑病（Celia's encephalopathy），可能与全身性脂肪营养不良有关，也可能无关，由c.985C>T变异引起。这种胞嘧啶到胸腺嘧啶的转变产生了一个隐蔽的剪接区，导致外显子7内含子化，产生一种异常形式的丝蛋白，即西莉亚丝蛋白（Celia seipin）。有人提出，这种蛋白质在内质网和神经元细胞核中的积累可能是这种神经退行性疾病的致病机制。近年来，已报道了 中与全身性脂肪营养不良和进行性癫痫性脑病相关的其他变异。有趣的是，这些变异中的大多数也可能导致外显子7缺失。在本综述中，我们分析了西莉亚脑病的分子基础及其致病机制、不同变异的临床特征以及一种治疗方法，以减缓这种致命神经系统疾病的进展。
