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Neurobiol Aging. 2014 Oct;35(10):2419.e23-2419.e25. doi: 10.1016/j.neurobiolaging.2014.04.010. Epub 2014 Apr 18.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia.

Le Ber I#1,2,3,4,5, De Septenville A#1,2,3, Guerreiro R#6, Bras J6, Camuzat A1,2,3, Caroppo P1,2,3, Lattante S1,2,3, Couarch P1,2,3, Kabashi E1,2,3, Bouya-Ahmed K1,2,3, Dubois B1,2,3,4,5, Brice A1,2,3,5,7.

Author information

1
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1127, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France.
2
Université Pierre et Marie Curie Univ, Unité Mixte de Recherche_S975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France.
3
Centre National de Recherche Scientifique, Unité Mixte de Recherche_S7225, Paris, France.
4
Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Centre de Référence des Démences Rares, Paris, France.
5
Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Paris, France.
6
Reta Lilla Weston Laboratories and Department of Molecular Neuroscience, Institute of Neurology London, London, England.
7
Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Département de Génétique et Cytogénétique, Unité Fonctionnelle de Neurogénétique Moléculaire et Cellulaire, Paris, France.
#
Contributed equally

Abstract

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 (20-50 years); (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.

KEYWORDS:

Alzheimer's disease; Dementia; FTD; FTLD; Nasu-Hakola; PLOSL; TREM2

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