These authors contributed equally to this work.
Mutation in Brief
Article first published online: 7 MAR 2007
© 2007 Wiley-Liss, Inc.
Volume 28, Issue 4, page 416, April 2007
How to Cite
van der Zee, J., Le Ber, I., Maurer-Stroh, S., Engelborghs, S., Gijselinck, I., Camuzat, A., Brouwers, N., Vandenberghe, R., Sleegers, K., Hannequin, D., Dermaut, B., Schymkowitz, J., Campion, D., Santens, P., Martin, J.-J., Lacomblez, L., De Pooter, T., Peeters, K., Mattheijssens, M., Vercelletto, M., Van den Broeck, M., Cruts, M., De Deyn, P. P., Rousseau, F., Brice, A. and Van Broeckhoven, C. (2007), Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum. Mutat., 28: 416. doi: 10.1002/humu.9484
Communicated by Jean-Louis Mandel
Online Citation: Human Mutation, Mutation in Brief #955(2007) Onlinehttp://www3.interscience.wiley.com/homepages/38515/pdf/955.pdf
- Issue published online: 7 MAR 2007
- Article first published online: 7 MAR 2007
- Manuscript Accepted: 19 JAN 2007
- Manuscript Received: 12 NOV 2006
- Cited By
- frontotemporal dementia;
- ubiquitin-positive inclusions;
- PGRN missense mutations;
- PGRN 5' sequence variations
Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin-positive brain pathology linked to chromosome 17 (FTDU-17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C>T, p.Pro248Leu and c.1294C>T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD. © 2007 Wiley-Liss, Inc.