Huang Qiong-hui, Xiao Jiang-xi, Wang Jing-min, Jiang Yu-wu, Wu Ye
Department of Pediatrics, First Hospital, Peking University, Beijing, China.
Zhonghua Er Ke Za Zhi. 2012 Jan;50(1):50-5.
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.
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.
(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.
This is the first report on LBSL patient and DARS2 mutation in China. p.Gly222Asp mutation is a novel mutation not reported around the world yet.
伴脑干和脊髓受累及乳酸升高的白质脑病（LBSL）是一种罕见的常染色体隐性疾病。受影响个体在DARS2基因中两个突变位点总是处于复合杂合状态。中国大陆尚无LBSL患者的报道。本研究旨在探讨一个LBSL家系的临床和遗传特征，这可能有助于中国对这种罕见疾病进行明确诊断、遗传咨询和产前诊断。
收集先证者及其他家庭成员的临床资料和DNA样本。分析包括症状、体征和头颅磁共振成像（MRI）在内的临床特征。采用聚合酶链反应（PCR）扩增DARS2基因的全部17个外显子及外显子 - 内含子边界，并对基因组DNA进行直接测序。通过对PCR扩增片段进行DNA限制性内切酶消化来证实突变。
（1）LBSL患者的临床特征包括缓慢进展的小脑共济失调和痉挛，神经功能障碍累及下肢多于上肢，且在脑和脊髓MRI上观察到特征性异常。（2）鉴定出两个突变，一个是DARS2基因外显子8中的新错义突变[c.665 G > A（p.Gly222Asp）]，另一个（c.228 - 16 C > G）位于DARS2基因内含子3中。
这是中国关于LBSL患者及DARS2突变的首次报道。p.Gly222Asp突变是一种尚未在全球报道过的新突变。
