ASPA基因新变异型致卡纳万病1例报道并文献复习

Canavan disease caused by a novel variant of ASPA gene:a case report and literature review

目的探讨卡纳万病(CD)的临床表现及天冬氨酸酰基转移酶(ASPA)基因变异特征,为临床工作中更好地识别该病提供参考。方法回顾性分析1例经基因检测诊断为CD的患儿临床资料,结合目前CD的研究进展进行文献复习。结果该病例为1例7个月男婴,以精神运动发育迟缓为主要临床表现,尿串联质谱检测显示N-乙酰天冬氨酸明显增高,头颅磁共振提示双侧额顶叶脑白质区见多发点状及小条形异常信号,符合脑白质病磁共振表现。二代基因测序发现患儿ASPA基因外显子区域存在c.432+1G>A和c.634+1G>A两处杂合变异,导致氨基酸改变。Sanger测序验证结果显示2个突变分别来源于母亲和父亲,为复合杂合变异,其中c.634+1G>A突变为首次报道。结论该例报道扩大了CD患儿的基因变异谱。

Objective To investigate the clinical manifestations of Canavan disease(CD)and the characteristics of aspartate acyltransferase(ASPA)gene mutations,in order to provide references for better identification of the disease in clinical work.Methods The clinical data of a child diagnosed with CD by genetic testing was retrospectively analyzed,and literature review was conducted.Results The case was a July baby boy with mental retardation as the main clinical manifestation.Urine tandem mass spectrometry showed that N-acetylaspartic acid levels significantly increased,cranial magnetic resonance imaging showed a multiple spotty and small abnormal signal changes in the cerebral white matter of bilateral frontal and parietal lobes.Second-generation gene sequencing revealed that there were two heterozygous mutations in c.432+1G>A and c.634+1G>A in the exon region of the child′s ASPA gene,leading to amino acid changes.The results of Sanger sequencing showed that the two mutations were derived from mother and father respectively,and they were compound heterozygous mutations,of which the c.634+1G>A mutation was the first report.Conclusion This report expands the spectrum of genetic variation in children with CD.