中文摘要：

目的对临床确诊为白质消融性白质脑病（VWM）的33例患儿进行遗传学分析，探讨中国VWM患儿基因型特点并为中国VWM患儿提供基因诊断策略。方法以2006年9月至2013年7月临床诊断为VWM的33例患儿为研究对象，对其EIF281—5基因外显子及外显子与内含子交界区进行基因测序及拷贝数异常检测；采用等位基因特异性聚合酶链反应（PCR）方法验证患者中的常见突变E1F283c．1037T〉C（P．Ile346Thr）是否为创始者突变。结果1．本组33例患儿基因突变阳性29例，阳性率与国外报道一致（88％比90％）。2．共发现EIF281-5突变32种，其中23种为国外未报道的新突变，以错义突变为主。3．患者突变谱与国外报道不同：29例基因突变阳性患儿中EIF285突变占38％（11／29例），EIF283突变占31％（9／29例），EIF284突变占17％（5／29例），EIF282突变占10％（3／29例），EIF281突变占3％（1／29例），其中EIF283突变患者所占比率明显高于国外报道（4％）。4．等位基因特异性PCR显示包含EIF283基因c．1037T〉C突变位点的单倍体上下游各2200bp范围内有相同的单核苷酸多态性（SNPs）。结论EIF283突变的患儿在中国VWM患儿中所占比例明显高于白种人群（31％比4％），提示中国患儿有自己独特的突变构成谱。EIF283的c．1037T〉C为中国患者的创始者突变。

英文摘要：

Objective To analyze the genotype of Chinese patients clinically diagnosed with vanishing white matter disease （VWM） clinically and to provide the genetic diagnostic strategy for children with VWM. Methods Thirty-three Chinese patients were sequenced in the coding regions and splice sites of E1F2B1-5. Copy number variations （CNVs） were tested in mutation negative patients. Among the 9 patients who carried mutations in eIF2Bγ,7 cases （78% ,7/9 cases） harbored at least one copy of the c. 1037T 〉 C（ p. Ile346Thr）. The nature of founder mutation was suspected and determined by allele-specific PCR. Results 1. Mutations in EIF2B1-5 were identified in 29 cases （88% ,29/33 cases） ,which was compared with the data from Caucasian patients （88% vs 90% ）. 2. Thirty-two different mutations were identified, consisting of 23 novel and 9 previously reported mutations. 3. The constituent ratio of patients was different from caucasian patients. In 29 mutation-positive children, E1F2B5 accounted for 38% （ 11/29 cases） ,EIF2B3 31% （9/29 cases） ,EIF2B4 17% （5/29 cases） ,EIF2B2 10% （3/29 cases） ,and EIF2BI accounted for 3% （1/29 cases）. Patients with E1F2B3 mutations were more common in Chinese patients. 4. The SNPs on the mutant allele amplified by allele specific PCR were compared among all the patients who harbored the EIF2B3-c. 1037T 〉 C mutation. Within 2 200 bp up and down stream surrounding the c. 1037, all the mutant alleles shared the same SNPs. Conclusions The percentage of Chinese patients with EIF2B3 mutation is much higher than that of Caucasian population （31% vs 4% ）, indicating that Chinese children with VWM have unique spectrum of mutations. EIF2B3-c. 1037T 〉 C is the founder mutations in Chinese patients.