Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis Academic Article


  • © 2014 Patiño et al.The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease. Copyright:

publication date

  • 2014/10/15


  • Age of Onset
  • Ceroid
  • Ceroid Lipofuscinosis, Neuronal, 6
  • Cognitive Dysfunction
  • Computer Simulation
  • Dementia
  • Deterioration
  • Disease Progression
  • Epilepsy
  • Exome
  • Genes
  • Genetics
  • Life Expectancy
  • Molecular Biology
  • Mutation
  • Myoclonus
  • Neurodegenerative Diseases
  • Neuronal Ceroid-Lipofuscinoses
  • Phenotype
  • Siblings
  • dementia
  • deterioration
  • disease course
  • epilepsy
  • genes
  • molecular genetics
  • mutation
  • neurodegenerative diseases
  • phenotype
  • signs and symptoms (animals and humans)
  • taxonomy

International Standard Serial Number (ISSN)

  • 1932-6203