Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21

Abstract summary

Co-discovered with Baker et al. that heterozygous loss-of-function mutations in GRN cause FTLD-U (frontotemporal lobar degeneration with ubiquitin inclusions). Demonstrated that progranulin haploinsufficiency is sufficient to cause disease. Established GRN as the second major FTD gene after MAPT.

Evidence labels

Therapeutic relevance

Co-founding paper for GRN-FTD genetics; companion to Baker et al. 2006, both establishing GRN replacement as a therapy rationale.