PPT1基因复合杂合变异致青少年型神经元蜡样脂褐质沉积症1例患儿的研究  

Study of a case of Juvenile neuronal ceroid lipofuscinosis due to compound heterozygous variants of PPT1 gene

作　　者：张丹 许芳[1] 包翌 徐严明[1] Zhang Dan;Xu Fang;Bao Yi;Xu Yanming(Department of Neurology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西医院神经内科,成都610041

出　　处：《中华医学遗传学杂志》2024年第12期1469-1472,共4页Chinese Journal of Medical Genetics

基　　金：四川省重点研发计划(2023YFS0270)。

摘　　要：目的报告并分析1例PPT1基因复合杂合变异所致的青少年型神经元蜡样脂褐质沉积症(NCL)患儿。方法选取2021年4月因"智能减退、行为异常5+年,运动障碍1+年"就诊于四川大学华西医院神经内科的1例青少年型NCL患儿作为研究对象,收集其相关临床资料,对其进行家系全外显子组检测(WES),并进行追踪随访。本研究通过了四川大学华西医院医学伦理委员会审查[批准号:2024年审(2286)号〕]。结果患儿为13岁男性,8岁起出现进行性智力减退、行为异常和运动障碍。脑电图提示异常背景活动,MRI提示脑萎缩。WES检测发现其PPT1基因存在父源性c.272(exon3)A>C以及母源性c.176(exon2)A>G复杂杂合变异,后续随访患儿上述症状逐渐加重,并出现癫痫发作,其表现符合既往报道的PPT1基因变异所致的青少年型NCL。结论PPT1基因c.272(exon3)A>C与c.176(exon2)A>G复杂杂合变异可能导致青少年型NCL。该病例既往国内未见报道,c.176(exon2)A>G变异亦属于首次报道。objectiveTo report and analyze a case of Juvenile neuronal ceroid lipofuscinosis(NCL)due to compound heterozygous variants of PPT1 gene.MethodsA child who was admitted to the Department of Neurology of West China Hospital of Sichuan University in April 2021 due to"intellectual decline and behavioral abnormalities for more than 5 years and movement disorder for more than 1 year"was selected as the study subject.Clinical data of the child was collected.Trio-whole exome sequencing was carried out for the child and his parents,and clinical follow-up was conducted.This study has been approved by the Medical Ethics Committee of West China Hospital of Sichuan University(Ethic No.2024-2286).ResultsThe patient,a 13-year-old male,showed progressive mental decline,behavioral abnormalities,and movement disorders from the age of 8.Electroencephalogram showed abnormal background activities,and magnetic resonance imaging showed brain atrophy.Trio-whole exome sequencing revealed that he had harbored a paternally derived heterozygous c.272(exon3)A>C variant and a maternally derived heterozygous c.176(exon2)A>G variant of the PPT1 gene.His presentation was in keeping with previously reported juvenile NCL due to variants of the PPT1 gene.ConclusionThe c.272(exon3)A>C and c.176(exon2)A>G compound heterozygous variants of the PPT1 gene probably underlay the Juvenile NCL in this child.Discovery of the c.176(exon2)A>G variant has expanded the mutational spectrum of this disease.

关 键 词：神经元蜡样脂褐质沉积症 青少年型 PPT1基因 变异 

分 类 号：R748[医药卫生—神经病学与精神病学]