A Study Of Neuronal Ceroid Lipofuscinosis CLN5 Gene Mutation And Literature Review

Background: Neuronal ceroid lipofuscinosis(NCLs)is a childhood autosomal recessive hereditary disease.It mainly occurs in northern Europe and North America,and the incidence is around 1:100000 worldwide.The common clinical symptoms of the diseases are progressive cognitive and motor development regression,seizures,visual impairment and dementia and its typical pathological features are characterized by accumulation of ceroid or lipofuscin-like autofluorescent materials in neurons retinal cells,lymphocytes,skin and other cell types.There are 14 genes have been identified relating to LINCL,one of which is Ceroid-lipofuscinosis neuronal protein 5(CLN5),a soluble lysosomal glycoprotein.Methods: We analyzed the clinical features and examinational results of 3Chinese children from two families who were diagnosed with LINCLs and obtained peripheral blood from the patients and their family members,then extracted genomic DNA from these blood samples.We randomly collected 200 children samples and extracted their genomic DNA from peripheral blood.We also performed a systematic review of literature on CLN5 related LINCLs patients.Results: We found three novel homozygous mutations including one small deletion mutation CLN5.c718 719delAT(p.Met240Valfs*13)is inherited from both parents and two missense mutations c.1082T>C(p.Phe361Ser),and c.623G>A(p.Cys208Tyr),these 3 mutations were not found in the 200 control group.We reviewed 278 papers about NCL resulting from CLN5 mutations and compared Chinese cases with 27 European and American cases.The overall onset age of European and American patients occur mainly at 3 to 6-year-old(66%,18/27),100%(27/27)of patients had psychomotor regression,and 99%(26/27)patients presented vision decline,70%(19/27)of patients suffered seizures.In China,the onset ages of 3 patients are 5 years old,as well as 1patient at 17 months old.4 Chinese patients presented psychomotor deterioration and seizures,only the collected patient had visual problems.Conclusion:(1)The CLN5 mutation due to the pathogenesis of NCL and related to racial diversity than previously reported more widely;(2)the study diagnosed 3 CLN5 mutation causing NCL Chinese patients and identified 3novel mutations in the 3 patients;(3)our understanding of the CLN5 mutation causing NCL is still insufficient.