机构：[1]Department of Neurology, National Centre for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China,临床科室泌尿外科小儿神经科首都医科大学附属北京儿童医院[2]Running Gene Inc., Beijing, China
Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c. 1551+1insTGAT in TPP1, c. 244G>T in CLN6, c. 554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.
基金：
Theodora Katsila, National Hellenic Research Foundation, Greece Fan Jin, Zhejiang University, China
第一作者机构：[1]Department of Neurology, National Centre for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China,
通讯作者：
通讯机构：[1]Department of Neurology, National Centre for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China,
推荐引用方式(GB/T 7714)：
Ren Xiao-Tun,Wang Xiao-Hui,Ding Chang-Hong,et al.Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis[J].FRONTIERS IN GENETICS.2019,10(APR):-.doi:10.3389/fgene.2019.00370.
APA：
Ren, Xiao-Tun,Wang, Xiao-Hui,Ding, Chang-Hong,Shen, Xiang,Zhang, Hao...&Fang, Fang.(2019).Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis.FRONTIERS IN GENETICS,10,(APR)
MLA：
Ren, Xiao-Tun,et al."Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis".FRONTIERS IN GENETICS 10..APR(2019):-
