CLN5基因复合杂合突变致青少年型神经元腊样脂褐质沉积症的临床特征及基因分析

目的报道及分析CLN5基因复合杂合突变致青少年型神经元腊样脂褐质沉积症(JNCL)患者的临床特征和基因突变类型。方法观察分析1例JNCL病人的临床表现、影像学、脑电图改变,进行全外显子组基因测序,并对其家庭成员进行相关基因检测和临床检查。结果患者于6岁开始视力减退及智力倒退,9岁出现肌阵挛发作、行走不稳。头颅MRI显示小脑明显萎缩,大脑皮质和脑干轻度萎缩。视频脑电图显示弥漫性2.5~3.5 Hz慢活动及颞区尖波。全外显子测序发现患者CLN5等位基因上1个来源于父亲的错义突变:exon2 c.376TC,以及1个来源于母亲的无义突变:exon3 c.595 CT。患儿父亲及弟弟均有c.376 TC突变,两人体查均发现水平性及旋转性眼震,该位点突变目前尚未见报道。结论 CLN5基因c.376TC和c.595CT的复合杂合突变可以引起JNCL临床症状、影像学和脑电图改变。对于NCL可疑病例应该对患者及家族成员及早进行相关基因测序明确其基因型,并实施生育指导。

Clinical features and gene analysis of juvenile neuronal ceroid lipofuscinosis induced by compound heterozygous mutation in CLN5 gene

Objective To investigate the clinical features and gene mutations of a patient with juvenile neuronal ceroid lipofuscinosis (JNCL) induced by compound heterozygous mutation in CLN5 gene.Methods The clinical manifestations,imaging findings,and electroencephalographic changes of one JNCL patient were observed,whole-exome sequencing was performed,and gene detection and clinical examination were performed for family members.Results The patient experienced visual deterioration and intellectual regression at the age of 6 years and presented myoclonic seizures and gait instability at the age of 9 years.Cranial MRI showed marked cerebellar atrophy and mild atrophy of the cerebral cortex and the brainstem,and video electroencephalogram showed diffuse 2.5-3.5 Hz slow activity and sharp waves in the temporal region.Whole-exome sequencing found one missense mutation (exon 2 c.376T ＞ C) from the father and one nonsense mutation (exon 3 c.595C ＞ T) from the mother in CLN5 gene.The c.376T ＞ C mutation was also detected in the patient's father and brother,who presented horizontal and rotational nystagmus.This mutation had not been reported.Conclusions The compound heterozygous mutations of c.376T ＞ C and c.595C ＞ T in CLN5 gene can cause the clinical symptoms,imaging findings,and electroencephalographic changes of JNCL.For patients suspected of JNCL,gene sequencing should be performed for these patients and their family members as early possible to determine their genotype and provide fertility guidance.