Contributed equally to this work.
Novel exon 1 progranulin gene variant in Alzheimer’s disease
Article first published online: 26 AUG 2008
© 2008 The Author(s). Journal compilation © 2008 EFNS
European Journal of Neurology
Volume 15, Issue 10, pages 1111–1117, October 2008
How to Cite
Cortini, F., Fenoglio, C., Guidi, I., Venturelli, E., Pomati, S., Marcone, A., Scalabrini, D., Villa, C., Clerici, F., Dalla Valle, E., Mariani, C., Cappa, S., Bresolin, N., Scarpini, E. and Galimberti, D. (2008), Novel exon 1 progranulin gene variant in Alzheimer’s disease. European Journal of Neurology, 15: 1111–1117. doi: 10.1111/j.1468-1331.2008.02266.x
- Issue published online: 5 SEP 2008
- Article first published online: 26 AUG 2008
- Received 30 April 2008 Accepted 23 June 2008
- allelic variant;
- Alzheimer’s disease;
- frontotemporal lobar degeneration;
Background and purpose: Progranulin (PGRN) expression is increased in activated microglia in Alzheimer's disease (AD) brain, suggesting a potential role in this pathology.
Methods: A mutation scanning of exons and flanking regions of PGRN was carried out in 120 patients with sporadic frontotemporal lobar degeneration and 145 with sporadic AD.
Results: Amongst variants not yet deposited, a novel allelic variant was identified in Exon 1 (g100169G > A). It leads to an amino acidic change (p.Gly35Arg) and was observed in a patient with late onset AD. In silico analysis predicted that this mutation is possibly damaging. A second variant (g.100165C > T), resulting in a silent mutation (pAsp33Asp), was found in a patient with semantic dementia and in another with early onset AD. Both variants were absent in 226 controls. In addition, two rare non-pathogenic variants lying very close to PGRN splice-site regions (IVS2 + 7G > A and IVS7 + 7G > A) were observed. Transcriptional analysis in peripheral blood mononuclear cells from patients demonstrated they do not affect exon splicing.
Conclusions: A novel putative PGRN mutation leading to an amino acidic substitution was identified in a patient with clinical AD.