Alpers-Huttenlocher Syndrome Russell P. Saneto, DO, PhD, Bruce H. Cohen, MD, William C. Copeland, PhD, Robert K. Naviaux, MD, PhD  Pediatric Neurology  Volume 48, Issue 3, Pages 167-178 (March 2013) DOI: 10.1016/j.pediatrneurol.2012.09.014 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Electroencephalogram segment from a 7-year-old girl with Alpers-Huttenlocher syndrome. Regional slowing in the parieto-occipital regions is demonstrated bilaterally, with epileptiform discharges within the right occipital region. The scale represents time (1-second intervals) and amplitude (microvolts). Pediatric Neurology 2013 48, 167-178DOI: (10.1016/j.pediatrneurol.2012.09.014) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 2 Functional and structural domains of the polymerase protein. (A) Linear organization of the polymerase-γ protein. The N-terminal domain (NTD) region comprises the mitochondrial targeting sequence, and is located at the N-terminal of the protein. The Thumb subdomains (Th) of the protein are evident between the exonuclease and linker region, as well as within the polymerase region [63]. The exonuclease domain contains essential motifs I, II, and III for its activity. The polymerase domain contains subdomains comprising the Thumb (Th), Palm, and Finger, which contain motifs A, B, and C, respectively. Two regions comprise the Palm subdomain within the polymerase domain. The motifs located within the polymerase domain are critical for polymerase activity [23,57]. Arrows indicate the numbered positions of amino acids that begin a subdomain. (B) Three-dimensional structure of the human DNA polymerase holoenzyme [59]. The color scheme of the polymerase-γ catalytic subunit is the same as in A, i.e., light blue for the polymerase domain, dark blue for the exonuclease region, red for the accessory interacting domain (AID) domain, and orange for the intrinsic processivity (IP) domain. The conserved motifs in the exonuclease (I, II, and III) and in the polymerase (A, B, and C) are charcoal-colored. The two accessory subunits are colored green for the proximal subunit, and grey for the distal subunit. Pediatric Neurology 2013 48, 167-178DOI: (10.1016/j.pediatrneurol.2012.09.014) Copyright © 2013 Elsevier Inc. Terms and Conditions