Volume 11, Issue 4, Pages 323-330 (April 2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study  Elisa Majounie, PhD, Alan E Renton, PhD, Kin Mok, MSc, Elise GP Dopper, Adrian Waite, PhD, Sara Rollinson, PhD, Adriano Chiò, MD, Gabriella Restagno, MD, Nayia Nicolaou, MSc, Javier Simon-Sanchez, PhD, Prof John C van Swieten, MD, Yevgeniya Abramzon, Janel O Johnson, PhD, Prof Michael Sendtner, MD, Roger Pamphlett, MD, Richard W Orrell, MD, Simon Mead, MD, Katie C Sidle, MD, Prof Henry Houlden, MD, Jonathan D Rohrer, MD, Prof Karen E Morrison, MD, Hardev Pall, MD, Prof Kevin Talbot, MD, Olaf Ansorge, MD, Dena G Hernandez, MSc, Sampath Arepalli, MS, Mario Sabatelli, MD, Gabriele Mora, MD, Massimo Corbo, MD, Fabio Giannini, MD, Andrea Calvo, MD, Elisabet Englund, MD, Giuseppe Borghero, MD, Gian Luca Floris, MD, Prof Anne M Remes, MD, Hannu Laaksovirta, MD, Leo McCluskey, MD, Prof John Q Trojanowski, MD, Vivianna M Van Deerlin, MD, Prof Gerard D Schellenberg, PhD, Michael A Nalls, PhD, Vivian E Drory, MD, Prof Chin-Song Lu, MD, Tu-Hsueh Yeh, MD, Hiroyuki Ishiura, MD, Yuji Takahashi, MD, Prof Shoji Tsuji, MD, Isabelle Le Ber, MD, Prof Alexis Brice, MD, Carsten Drepper, PhD, Nigel Williams, PhD, Janine Kirby, PhD, Prof Pamela Shaw, MD, Prof John Hardy, PhD, Pentti J Tienari, MD, Prof Peter Heutink, PhD, Huw R Morris, MD, Prof Stuart Pickering-Brown, PhD, Dr Bryan J Traynor, MD  The Lancet Neurology  Volume 11, Issue 4, Pages 323-330 (April 2012) DOI: 10.1016/S1474-4422(12)70043-1 Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 1 Finnish risk haplotypes across the chromosome 9p21 region in 262 patients with amyotrophic lateral sclerosis and the C9orf72 mutation The previously identified Finnish risk haplotype is shown below the graph (27 357 278–27 589 746 bp; NCBI build 36; 42 single nucleotide polymorphisms [SNPs]).16 Underneath the haplotype is a binary representation of the same data, with red circles at SNP positions where the haplotype has the less common allele at that site. In the graph, individual patients are shown as horizontal lines showing the extent to which they share the risk haplotype. The vertical black dashed line shows the location of the C9orf72 hexanucleotide repeat expansion. Recombination rates (centimorgans per megabase [cM/Mb]) from phase 2 Centre d'Etude du Polymorphisme Humain (CEPH) samples of HapMap are shown with a grey line. The Lancet Neurology 2012 11, 323-330DOI: (10.1016/S1474-4422(12)70043-1) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 2 Age-related penetrance of the GGGGCC hexanucleotide repeat expansion in C9orf72 Kaplan-Meier analysis of 603 mutant-gene carriers (212 patients with familial amyotrophic lateral sclerosis, 234 with sporadic amyotrophic lateral sclerosis, 99 with familial frontotemporal dementia, 53 with sporadic frontotemporal dementia, and five neurologically healthy controls). Age-related penetrance (ie, the proportion of mutant-gene carriers with manifestations of the disease by a given age) rose steadily, from 10% in patients younger than 45 years to almost 100% by the age of 80 years. The dotted lines shows the age at which 50% of the cohort developed symptoms. Vertical blue lines show censored events. The Lancet Neurology 2012 11, 323-330DOI: (10.1016/S1474-4422(12)70043-1) Copyright © 2012 Elsevier Ltd Terms and Conditions