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Title
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Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients
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Author
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Institution/Organisation
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BELNEU Consortium
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Abstract
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| 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 carriers 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. |
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Language
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English
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Source (journal)
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Neurobiology of aging. - Fayetteville, N.Y.
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Publication
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Fayetteville, N.Y.
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2013
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ISSN
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0197-4580
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DOI
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10.1016/J.NEUROBIOLAGING.2012.12.007
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Volume/pages
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34
:6
(2013)
, p. 1-5
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Article Reference
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1711.e1
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ISI
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000317417100031
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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