(1)背景:Cockayne综合征(CS)是一种超罕见的多系统疾病,经典细分为三种形式,其特征在于两个致病基因ERCC6(CSB型)和ERCC8(CSA型)的临床谱没有明确的基因型-表型相关性。我们对此进行了评估,介绍了一系列基因证实的CSB患者。(2)材料和方法:我们回顾性收集了人口学,临床,遗传,神经影像学,和CSB患者的血清神经丝轻链(sNFL)数据;还确定了诊断和严重程度评分。(3)结果:提供了8名ERCC6/CSB患者的数据。四名患者患有CSI,三名患者CSII,和一名CSIII患者。不同程度的共济失调和痉挛是主要的神经系统特征,具有可变组合的系统特征。诊断时的平均年龄低于II型,其中典型的CS征象更为明显。有趣的是,sNFL的测定似乎反映了临床分类。鉴定了两个新的过早终止密码子和一个新的错义变体。所有CSI受试者均具有p.Arg735Ter变体;较温和的CSIII受试者进行了p.Leu764Ser错觉变化。(4)结论:我们的工作证实了ERCC6/CSB类型的临床变异性,其中表现可能从严重受累于产前或新生儿发病到正常的精神运动发育,然后是进行性共济失调。我们提议,第一次在CS,sNFL作为一种有用的外周生物标志物,与目前可用的参考值相比,水平增加,并且具有反映疾病严重程度的潜在能力。
(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity.