title: Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients.
abstract: 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.
authors: Department of Molecular Genetics, VIB, Antwerp, Belgium.
authors: Lubina
authors: L
authors: Dillen
authors: Tim
authors: T
authors: Van Langenhove
authors: Sebastiaan
authors: S
authors: Engelborghs
authors: Mathieu
authors: M
authors: Vandenbulcke
authors: Stayko
authors: S
authors: Sarafov
authors: Ivailo
authors: I
authors: Tournev
authors: Celine
authors: C
authors: Merlin
authors: Patrick
authors: P
authors: Cras
authors: Rik
authors: R
authors: Vandenberghe
authors: Peter P
authors: PP
authors: De Deyn
authors: Albena
authors: A
authors: Jordanova
authors: Marc
authors: M
authors: Cruts
authors: Christine
authors: C
authors: Van Broeckhoven
authors: Julie
authors: J
authors: van der Zee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000071183:Autophagy-Related Proteins; D001530:Belgium / Q000453:epidemiology; D018797:Cell Cycle Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051304:Profilins / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins; C495738:PFN1 protein, human; D051304:Profilins; C405662:UBQLN2 protein, human; D014452:Ubiquitins