Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity - Archive ouverte HAL Access content directly
Journal Articles Blood Year : 2005

Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity

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Jerome Feldmann
  • Function : Author
Gaël Ménasché
  • Function : Author
  • PersonId : 995960
Veronique Minard-Colin
  • Function : Author
Brigitte Bader-Meunier
  • Function : Author
  • PersonId : 910470
Laurence Le Clainche
  • Function : Author
Marc Tardieu
  • Function : Author
  • PersonId : 935828
Geneviève de Saint Basile
  • Function : Author
  • PersonId : 912689

Abstract

Mutations in the perforin gene cause familial hemophagocytic lymphohistiocytosis (FHL). The first symptoms of FHL are usually intractable fever, hepatosplenomegaly, and pancytopenia. Most FHL patients subsequently develop central nervous system (CNS) manifestations due to infiltration of tissues by activated lymphocytes and macrophages. We report 2 FHL patients with an atypical phenotype characterized by isolated severe neurologic symptoms mimicking chronic encephalitis and leading to an early death. Functional and molecular analyses revealed the same novel missense mutation in the perforin gene in both patients; this mutation affected the calcium-binding domain of the protein. This missense mutation did not affect perforin maturation or expression in cytotoxic cells but impaired in vitro cytotoxic activity. Diagnosis was delayed in both patients because of the initial neurologic expression and the normal expression of perforin in circulating lymphocytes. This emphasizes the importance of early diagnosis of this atypical form of FHL, as CNS involvement causes severe, irreversible encephalopathy. This observation also raises the question of the role of some mutations in the neurologic expression of FHL.

Dates and versions

inserm-02440351 , version 1 (15-01-2020)

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Jerome Feldmann, Gaël Ménasché, Isabelle Callebaut, Veronique Minard-Colin, Brigitte Bader-Meunier, et al.. Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity. Blood, 2005, 105 (7), pp.2658-2663. ⟨10.1182/blood-2004-09-3590⟩. ⟨inserm-02440351⟩
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