巨脑性白质脑病伴皮质下囊肿一家系临床特征及基因突变分析

Analysis of clinical characteristics and gene mutations of megalencephalic leukoencephalopathy with subcortical cysts in a family

目的 分析巨脑性白质脑病伴皮质下囊肿（MCL）的临床特点及基因变异情况,探讨其遗传特点,为家庭提供遗传咨询.方法 收集患儿及其家系成员的临床资料,提取患儿及家系成员外周血DNA,采用目标序列捕获高通量测序技术和Sanger测序技术进行MLC1基因变异检测.结果 1.临床特点：婴儿期头围异常增大为首发症状;运动发育落后,并于学龄前期运动能力倒退,运动障碍逐渐进展,最终瘫痪;幼儿期出现癫痫;病程早期头颅磁共振成像显示双侧大脑半球白质弥散异常信号,伴颞叶囊性变,随病程进展出现脑萎缩.2.基因分析结果：先证者及胞姐的MLC1基因同时存在c.368C〉T（p.Thr123Ile）与c.353C〉T（p.Thr118Met）复合杂合变异;先证者之父及胞姐携带c.368C〉T（p.Thr123Ile）、患儿母亲携带c.353C〉T（p.Thr118Met）杂合变异,均为临床表型正常的携带者.结论 MCL是婴幼儿运动发育落后的病因之一,常以头围增大为首发症状.MLC1基因c.368C〉T（p.Thr123Ile）变异为MLC致病突变,且可能是本病又一个新突变.

Objective To analyze the clinical characteristics and genetic variation of megalencephalic leu-koencephalopathy with subcortical cysts（MCL）,then to explore the genetic characteristics so as to help families by pro-viding genetic counseling. Methods The clinical data of the children and their family members were collected,and the peripheral blood DNA of the children and family members were extracted. Then,the MLC1 gene mutation in the children was detected by using the target sequence capture high-throughput sequencing technology and Sanger sequencing tech-nology. Results （1）MCL often presented abnormal head circumference in infants as the first symptom. The main clini-cal manifestations were hypoevolutism in motor development,retrogression of early school age,then the movement disor-der progressed and finally paralyzed;epilepsy was common in early childhood;head magnetic resonance imaging showed white matter in bilateral cerebral hemisphere diffusing abnormal signal with temporal lobe cystic change in the early stage,and then showed brain atrophy. （2）The gene results showed that the 2 girls with MLC had both c. 368C 〉T （p. Thr123Ile）and c. 353C 〉 T （p. Thr118Met）complex heterozygous variation,which existed in the MLC1 gene. The girls′ father and a sister carried c. 368C 〉 T （p. Thr123Ile）,while the mother carried c. 353C 〉 T （p. Thr118Met） heterozygous variation,all of whom were normal phenotypes. Conclusions MCL is one cause of hypoevolutism in motor development in children and abnormal head circumference of infants is usually the first symptom. The MLC1 gene c. 368C〉 T（p. Thr123Ile）is a pathogenic mutation for MLC,and may be another new pa-thogenic mutation.