Reference number: OPUSeJ 201301232046DAA
Link: published article http://informahealthcare.com/doi/abs/10.3109/21678421.2012.758288
Title: Detection of a novel frameshift mutation and regions with homozygosis within ARHGEF28 gene in familial amyotrophic lateral sclerosis
Authors: Cristian A. Droppelmann 1, Jian Wang 2, Danae Campos-Melo 1, Brian Keller 1, Kathryn Volkening 1,3, Robert A. Hegele 2 & Michael J. Strong 1,3
Abstract: Rho guanine nucleotide exchange factor (RGNEF) is a novel NFL mRNA destabilizing factor that forms neuronal cytoplasmic inclusions in spinal motor neurons in both sporadic (SALS) and familial (FALS) ALS patients. Given the observation of genetic mutations in a number of mRNA binding proteins associated with ALS, including TDP-43, FUS/TLS and mtSOD1, we analysed the ARHGEF28 gene (approx. 316 kb) that encodes for RGNEF in FALS cases to determine if mutations were present. We performed genomic sequencing, copy number variation analysis using TaqMan real-time PCR and spinal motor neuron immunohistochemistry using a novel RGNEF antibody. In this limited sample of FALS cases (n=7) we identified a heterozygous mutation that is predicted to generate a premature truncated gene product. We also observed extensive regions of homozygosity in the ARHGEF28 gene in two FALS patients. In conclusion, our findings of genetic alterations in the ARHGEF28 gene in cases of FALS suggest that a more comprehensive genetic analysis would be warranted.
Author bio: N/A
Sponsor editor: N/A
1 Molecular Brain Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario
2 Vascular Biology Research Group, Robarts Research Institute, London, Ontario
3 Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
Correspondence: M. J. Strong, Room C7–120, University Hospital, LHSC, 339 Windermere Road, London, Ontario N6A 5A5, Canada. Fax: 1 519 663 3609. E-mail: Michael.Strong@Schulich.uwo.ca.
Keywords: Rho guanine nucleotide exchange factor, ARHGEF28, ALS, mutation, homozygosity, protein aggregates, neurofilament
Subject: Science/ genetics, amyotrophic lateral sclerosis
Bibliography: alphabetical N/A
Citation: Droppelmann, C A et al, 2013, “Detection of a novel frameshift mutation and regions with homozygosis within ARHGEF28 gene in familial amyotrophic lateral sclerosis”, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Posted online on January 4, 2013. doi:10.3109/21678421.2012.758288. http://informahealthcare.com/doi/abs/10.3109/21678421.2012.758288