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

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• 作者：Lubina Dillen^a ; ^b ; Tim Van Langenhove^a ; ^b ; ^c ; Sebastiaan Engelborghs^b ; ^d ; Mathieu Vandenbulcke^e ; ^f ; Stayko Sarafov^g ; Ivailo Tournev^g ; ^h ; Celine Merlin^a ; ^b ; Patrick Cras^b ; ^c ; Rik Vandenberghe^f ; ⁱ ; Peter P. De Deyn^b ; ^d ; ^j ; Albena Jordanova^a ; ^b ; ^k ; Marc Cruts^a ; ^b ; Christine Van Broeckhoven^a ; ^b ; Julie van der Zee^a ; ^b ; ^{julie.vanderzee@molgen.vib-ua.be} ; BELNEU consortium ¹
• 关键词：UBQLN2 ; PFN1 ; FTLD ; ALS
• 刊名：Neurobiology of Aging
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：34
• 期：6
• 页码：1711.e1-1711.e5
• 全文大小：336 K

文摘

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.