神经元蜡样脂褐质沉积症3例临床及基因变异分析

Analysis on the clinical manifestations and gene mutations from 3 cases with neuronal ceroid lipofuscinosis

目的探讨神经元蜡样脂褐质沉积症(NCL)的临床和基因变异特征。方法回顾分析3例NCL患儿的临床资料和基因检测结果。结果3例女性患儿,多表现为认知和运动倒退、不同程度的癫痫发作、视力受累。全外显子测序发现,例1的PPT1基因存在c.124+1G>A及c.413C>T复合杂合变异,其中c.124+1G>A遗传自父亲,c.413C>T遗传自母亲;例2及其哥哥PPT1基因存在c.181C>T及c.536+1G>A复合杂合变异,其中c.181C>T遗传自父亲,c.536+1G>A遗传自母亲;例3的CLN8基因存在c.768G>T及c.209G>T复合杂合变异,其中c.768G>T遗传自父亲,c.209G>T遗传自母亲。c.768G>T和c.209G>T是既往未见报道的新的变异位点。结论基因检测有助NCL的诊断及遗传咨询;PPT1基因变异可呈现不同的临床表现,即使是同一家系具有相同变异位点的个体临床表现也各不相同。

Objective To explore the clinical and genetic characteristics of children with neuronal ceroid lipofuscinosis(NCL).Methods Clinical data of three patients diagnosed with NCL was retrospectively analyzed.Genomic DNA from peripheral blood samples from 3 families of the neuronal ceroid lipofuscinosis were extracted,and whole exome sequencing(WES)was used to identify mutations.Results The affected members of the three families presented with cognitive and motor regression,seizures of various degrees and visual impairment.Compound heterozygous mutations of c.124+1 G>A inherited from her father and c.413 C>T inherited from her mother in PPT1 gene were found by the WES in case one.In case two,a compound heterozygous mutation of c.181 C>T and c.536+1 G>A in PPT1 gene were found in her and her brother,in which c.181 C>T mutation was inherited from her father and c.536+1 G>A mutation was inherited from her mother.Compound heterozygous mutations of c.768 G>T inherited from her father and c.209 G>T inherited from her mother in CLN8 gene were found in patient 3.c.768 G>T and c.209 G>T mutation were new mutation site not reported before.Conclusion Patients with PPT1 gene mutation may present with different clinical manifestation,even if in the individual with same mutation from the same family;the findings enriched the pathogenic mutation spectrum of CLN8.