Cockayne综合征1例临床及ERCC8基因突变特征

A case of Cockayne syndrome caused by ERCC8 gene mutation

目的探讨Cockayne综合征患儿的临床、影像学和ERCC8基因突变特征。方法回顾分析1例经基因检测确诊的Cockayne综合征患儿的临床和影像学资料,应用目标序列捕获和第二代测序技术检测患儿相关基因,采用Sanger测序验证突变位点的结果,并对其父母、姐姐样本进行突变位点的序列分析。结果女性患儿,7岁,主要临床表现为精神运动发育迟滞、生长发育障碍、特殊面容、光敏性皮炎、痉挛性瘫痪、小脑共济失调。头颅磁共振显示双侧半卵圆中心、脑室旁白质对称脱髓鞘改变,小脑萎缩。二代测序结果显示患儿ERCC8基因外显子区域两处杂合突变点c.397C>T和c.394_398del,分别引起氨基酸变化p.Q133X和p.L132fs;Sanger测序结果显示2个突变分别来源于母亲和父亲,为复合杂合突变。c.394_398del位点为已报道致病突变,c.397C>T为首次报道。结论二代测序技术可准确检测Cockayne综合征的ERCC8基因突变。首次发现c.397C>T突变位点,扩大了中国Cockayne综合征患者的基因突变谱。

Objective To explore the clinical, radiological and gene mutation features ofERCC8 gene in one patient with Cockayne syndrome. Methods Clinical and radiological data of a girl diagnosed with Cockayne syndrome through gene detection were retrospectively analyzed. Next-generation sequencing was used to detect genetic cause. Sanger sequencing was used to confirm the candidate variants and detect mutations in her parents and sister. Results The patient showed psychomotor retardation, growth failure, special face, and light sensitivity. Neurological examination revealed noticeable developmental delay, motor impairment, spastic paralysis, and cerebellar ataxia. Brain MRI revealed symmetrical demyelination of bilateral centrum semiovale and periventricular white matter. The cerebellum was atrophic. The patient was found to have compound heterozygous mutations ofc.397C〉T（p.Q133X） and c.394 398del（p.L132fs）. Sanger sequencing showed these two mutations were inherited from her mother and father respectively. Conclusions Next-generation sequencing technology is a useful tool for the detection of mutation in ERCC8 gene, which is valuable for the diagnosis of Cockayne syndrome. These two mutations expanded the mutation spectrum of Cockayne syndrome in Chinese population.