Canavan病一例临床和天冬氨酸酰基转移酶基因突变分析

Clinical and aspartoacylase gene mutation analysis of Canavan disease in a child

目的探讨Canavan病的临床和天冬氨酸酰基转移酶(ASPA)基因突变特征。方法回顾分析1例2018年6月于郑州大学附属儿童医院神经内科就诊且经基因检测确诊的Canavan病患儿的临床资料。结果患儿女性,1岁5个月,主要临床表现为精神运动发育倒退、肌张力高、腱反射亢进;尿代谢筛查N-乙酰天冬氨酸明显增高(检测值66.832 7,为正常值的60余倍);头颅磁共振成像示脑内多发对称性斑片状异常信号,符合脑白质病磁共振表现,考虑代谢性疾病。应用目标序列捕获和新一代测序检测发现患儿ASPA基因外显子区域存在c.79_80del和c.554G>T两处杂合突变,分别引起氨基酸变化p.Gly27Arg和p. Gly185Val;Sanger测序验证结果显示2个突变分别来源于父亲和母亲,为复合杂合突变,其中c.554G>T突变为首次报道。结论新一代测序技术可准确检测ASPA基因突变,可作为Canavan病的首选确诊手段。本报道扩大了Canavan病患儿的基因突变谱。

Objective To investigate the clinical and aspartoacylase (ASPA) gene mutation characteristics of Canavan disease. Methods The clinical data of a child with Canavan disease diagnosed by gene detection who visited Children′s Hospital Affiliated to Zhengzhou University in June 2018 were reviewed and analyzed. Results A one year and five months old girl presented with psychomotor retrogression, hypermyotonia, and tendon hyperreflexia. The urinary N-acetylaspartic acid levels were significantly higher (66.832 7, more than 60 times that of normal individuals). Magnetic resonance imaging of the brain showed a multiple and symmetrical hyperintense signal changes in the cerebral white matter. Two heterozygous mutations c.79_80del (p.Gly27Arg) and c.554G>T (p.Gly185Val) were screened by targeted next generation sequencing. The results of Sanger sequencing showed the two mutations were compound heterozygous mutation derived from her father and mother, and the mutation c.554G>T has never been reported. Conclusions The next generation sequencing can accurately detect ASPA gene mutation as the first choice for the diagnosis of Canavan disease. The mutation c.554G>T enriches the gene mutation spectrum of Canavan disease.