Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

Isabelle Le Ber, Anne De Septenville, Rita Guerreiro, José Bras, Agnès Camuzat, Paola Caroppo, Serena Lattante, Philippe Couarch, Edor Kabashi, Kawtar Bouya-Ahmed, Bruno Dubois, Alexis Brice

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TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20-50years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging.

Original languageEnglish
JournalNeurobiology of Aging
Issue number10
Publication statusPublished - 2014


  • Alzheimer's disease
  • Dementia
  • FTD
  • FTLD
  • Nasu-Hakola
  • TREM2

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Medicine(all)


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