Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients

Neurobiol Aging. 2013 Jun;34(6):1711.e1-5. doi: 10.1016/j.neurobiolaging.2012.12.007. Epub 2013 Jan 9.


UBQLN2 and PFN1 were recently associated with amyotrophic lateral sclerosis (ALS). We investigated a role for these ALS genes in frontotemporal lobar degeneration (FTLD). We screened 328 FTLD, 17 FTLD-ALS, and 157 ALS patients. Patients originated from Flanders-Belgium except for 26 Bulgarian ALS patients. The frequency of UBQLN2 and PFN1 genetic variants in the FTLD patients was low at 0.30% and 0.91% respectively. Moreover, the biological relevance to disease of the variants was questionable. In UBQLN2, we identified p.S346C outside of the PXX domain in 1 FTLD patient. Yet, a closely located serine substitution, p.S340I, was observed in a neurologically healthy control individual. In PFN1, we observed the previously reported p.E117G mutation in 3 FTLD patients and in 3 control individuals. In the ALS patient cohort, we detected UBQLN2 variants in 1.27% of patients. These involved 2 novel UBQLN2 missense mutations, p.S400G and p.P440L, that were also present in unaffected relatives (i.e., the p.S400G carrier's son [70 years] and daughter [65 years]) and the p.P440L carrier's mother (67 years). No mutations were observed in PFN1. In summary, we conclude that genetic variations in UBQLN2 and PFN1 in a predominantly Flanders-Belgian cohort of FTLD and ALS patients are extremely rare.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Amino Acid Sequence
  • Autophagy-Related Proteins
  • Belgium / epidemiology
  • Cell Cycle Proteins / genetics*
  • Cohort Studies
  • Female
  • Frontotemporal Lobar Degeneration / diagnosis
  • Frontotemporal Lobar Degeneration / epidemiology*
  • Frontotemporal Lobar Degeneration / genetics*
  • Genetic Testing / methods*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Profilins / genetics*
  • Ubiquitins / genetics*


  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Cell Cycle Proteins
  • PFN1 protein, human
  • Profilins
  • UBQLN2 protein, human
  • Ubiquitins