A novel deletion in progranulin gene is associated with FTDP-17 and CBS

Neurobiol Aging. 2008 Mar;29(3):427-35. doi: 10.1016/j.neurobiolaging.2006.10.028. Epub 2006 Dec 6.


In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent. Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound differences in the biological functions of the encoded proteins, it is not possible to define a clinical phenotype distinguishing the disease caused by mutations in MAPT and PGRN genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chromosomes, Human, Pair 17*
  • DNA Mutational Analysis
  • Dementia / diagnostic imaging*
  • Dementia / genetics*
  • Exons / genetics
  • Family Health*
  • Female
  • Genetic Linkage
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Italy
  • Leucine / genetics
  • Male
  • Microsatellite Repeats / genetics
  • Progranulins
  • Sequence Deletion*
  • Tomography, Emission-Computed, Single-Photon / methods


  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Leucine