中文摘要：

目的探讨一个伴脊髓、脑干受累，脑白质乳酸升高的脑白质病（LBSL）家系的临床和影像学特点，并检测其致病基因DARS2的突变情况。方法收集并分析先证者的临床资料，应用PCR方法对DARS2基因的所有17个外显子及其外显子内含子连接区域进行扩增，采用DNA直接测序与DNA限制性内切酶酶切、100条正常染色体对照验证的方法进行DARS2基因突变检测。结果（1）临床特点：先证者发病年龄为14岁，以运动倒退、走路姿势异常起病，下肢运动障碍重于上肢，智力基本正常，头颅核磁及磁共振波谱（MRS）符合LBSL特点。（2）基因突变分析：先证者DARS2基因发现第8外显子C．665G〉A（P．Gly222Asp）与第2内含子C．228—16C〉G，首次证实了我国LBSL患者中存在DARS2基因突变。家系突变分离研究结果表明，c．665G〉A（P．Gly222Asp）来自其父亲，c．228—16C〉G突变则来源于其母亲，其兄携带C．228—16C〉G，父母及其兄均为表型正常的携带者，符合常染色体隐性遗传规律。结论在国内诊断第1例LBSL病，明确了该家系中的致病基因突变及相关个体基因状况，为该家庭进行准确的遗传咨询提供了可能。

英文摘要：

Objective Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation （LBSL） is a rare autosomal recessive disease. Affected individuals are invariably compound heterozygous for two mutations in DARS2. No reports of LBSL patients have been published in the mainland of China. The aim of this study was to explore the clinical and genetic features of a family with LBSL, which may contribute to definite diagnosis, genetic counseling and prenatal diagnosis of this rare disease in China. Methods Clinical data of the proband and other family members as well as DNA samples were collected. Clinical features including symptoms, signs and cranial MRI were analyzed. All 17 exons and exon-intron boundaries of DARS2 gene were amplified with polymerase chain reaction （PCR） and directly sequenced for genomic DNA. The mutation was proved by DNA restriction enzyme digestion of PCR-amplified fragments. Results （ 1 ） The clinical features of patient with LBSL included slowly progressive cerebellar ataxia and spasticity, the neurologic dysfunction involving the legs more than the arms, and with characteristic abnormalities observed on brain and spinal cord MRI. （2） Two mutations were identified, one was a novel missense mutation [ c. 665 G 〉 A（p. Gly222Asp） ] in DARS2 gene exon 8, the other （ c. 228-16 C 〉 G） was in DARS2 gene intron 3. Conclusion This is the first report on LBSL patient and DARS2 mutation in China. p. Gly222Asp mutation is a novei mutation not reported around the world yet.