Extensive white matter involvement in patients with frontotemporal lobar degeneration: Think progranulin

Paola Caroppo, Isabelle Le Ber, Agnès Camuzat, Fabienne Clot, Lionel Naccache, Foudil Lamari, Anne De Septenville, Anne Bertrand, Serge Belliard, Didier Hannequin, Olivier Colliot, Alexis Brice

Research output: Contribution to journalArticlepeer-review


IMPORTANCE: Mutations in the progranulin (GRN) gene are responsible for 20% of familial cases of frontotemporal dementias. All cause haploinsufficiency of progranulin, a protein involved in inflammation, tissue repair, and cancer. Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes.We describe 4 GRN mutation carriers with remarkable widespread white matter lesions (WML) associated with lobar atrophy shown on magnetic resonance imaging. OBSERVATIONS: Four GRN mutation carriers (age at onset, 56-65 years) presenting with severe WML were selected from 31 GRN mutation carriers who were followed up in our dementia centers. The WML were predominantly in the frontal and parietal lobes and were mostly confluent, affecting the periventricular subcortical white matter and U-fibers. In all patients, common vascular,metabolic, inflammatory, dysimmune, and mitochondrial disorders were excluded and none had severe vascular risk factors. CONCLUSIONS AND RELEVANCE: Our data suggest that white matter involvement may be linked to progranulin pathological processes in a subset of GRN mutation carriers. The plasma progranulin measurement, which is predictive of GRN mutations, and GRN sequencing should thus be included in investigations of patients with frontotemporal lobar degenerations who show unusual white matter hyperintensities and atrophy on magnetic resonance imaging.

Original languageEnglish
Pages (from-to)1562-1566
Number of pages5
JournalJAMA Neurology
Issue number12
Publication statusPublished - Dec 1 2014

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Medicine(all)


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