Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage Katherine R. Smith, John Damiano, Silvana Franceschetti,

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Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage Katherine R. Smith, John Damiano, Silvana Franceschetti, Stirling Carpenter, Laura Canafoglia, Michela Morbin, Giacomina Rossi, Davide Pareyson, Sara E. Mole, John F. Staropoli, Katherine B. Sims, Jada Lewis, Wen-Lang Lin, Dennis W. Dickson, Hans-Henrik Dahl, Melanie Bahlo, Samuel F. Berkovic The American Journal of Human Genetics Volume 90, Issue 6, Pages 1102-1107 (June 2012) DOI: 10.1016/j.ajhg.2012.04.021 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 Family Pedigree and Clinical Features of NCL in Proband (A) Pedigree of family (arrow indicates proband) indicating mutation status for GRN (c.813_816del). Plasma progranulin values are shown in red (ng/ml; median normal value is 126 ng/ml). (B) Retinal photograph of proband showing optic atrophy, arteriolar attenuation, and irregular retinal pigmentation. (C) Electron micrograph of skin biopsy from the proband. Typical fingerprint profiles within a membrane-bound structure in an eccrine pale cell are shown. The bar indicates 100 nm. The American Journal of Human Genetics 2012 90, 1102-1107DOI: (10.1016/j.ajhg.2012.04.021) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 Results of Linkage Analysis Autosomal genome-wide LOD scores, adjusted for inbreeding, for the family under a fully penetrant recessive genetic model. The American Journal of Human Genetics 2012 90, 1102-1107DOI: (10.1016/j.ajhg.2012.04.021) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 NCL Pathology in Progranulin-Deficient Mice Electron micrograph showing a high-power view of one of the storage granules in a neuron from the habenula of a Grn−/− mouse. The pattern corresponds to the rectilinear complex, which, along with fingerprint profiles, is characteristic of most types of NCL. The arrow points to a pentalaminar profile. The bar indicates 100 nm. The American Journal of Human Genetics 2012 90, 1102-1107DOI: (10.1016/j.ajhg.2012.04.021) Copyright © 2012 The American Society of Human Genetics Terms and Conditions