Clinico-pathological manifestations of variant late infantile neuronal ceroid lipofuscinosis (vLINCL) caused by a novel mutation in MFSD8 gene

Hanna Mandel, Ksenya Cohen Katsanelson, Morad Khayat, Ilana Chervinsky, Eugene Vladovski, Theodor C. Iancu, Margarita Indelman, Yoseph Horovitz, Eli Sprecher, Stavit A. Shalev, Ronen Spiegel

Research output: Contribution to journalArticlepeer-review


Neuronal ceroid lipofuscinosis (NCL) refers to a growing heterogeneous group of neurodegenerative disorders characterized by lysosomal accumulation of abnormal autofluorescent material. NCLs are traditionally classified clinically according to their age of onset. Variable late infantile NCL (vLINCL) is the most genetically heterogeneous subtype as it has been shown to be caused by mutations in at least six genes. We report on 5 patients of a consanguineous family who presented in early childhood with intractable seizures, severe cognitive and motor decline, behavioral impairment and progressive retinal degeneration. Disease course was severe; all patients were in a vegetative state by the second decade of life, and eventually die prematurely (except in one case). Ultrastructural studies of brain and rectal mucosa disclosed accumulation of storage material in various patterns including fingerprint, curvilinear, and granular osmiophilic deposits consistent with the diagnosis of NCL. Brain pathologic features from a living patient are first reported here and shed light on disease progression and pathogenesis. Using a combination of whole genome autozygosity mapping and candidate gene direct sequencing, we identified a mutation in MFSD8, c.472G>A (p.Gly158Ser), which was found to segregate with the disease phenotype in the family.This study underscores the importance of a combined clinic-molecular workup in NCLs and other neurodegenerative conditions.

Original languageEnglish
Pages (from-to)607-612
Number of pages6
JournalEuropean Journal of Medical Genetics
Issue number11-12
StatePublished - 1 Nov 2014


  • Autosomal recessive
  • Lysosomal storage
  • Neuronal ceroid lipofuscinosis
  • Retinal degeneration


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