@article{discovery1358290,
           month = {June},
          number = {6},
         journal = {The American Journal of Human Genetics},
           title = {Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage.},
            year = {2012},
            note = {This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PMCID: PMC3370276},
          volume = {90},
           pages = {1102 -- 1107},
        keywords = {Animals, Chromosome Mapping, DNA Mutational Analysis, Dementia, Family Health, Female, Genetic Linkage, Heterozygote, Homozygote, Humans, Intercellular Signaling Peptides and Proteins, Lod Score, Male, Mice, Mutation, Pedigree, Phenotype},
            issn = {0002-9297},
        abstract = {We performed hypothesis-free linkage analysis and exome sequencing in a family with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two linkage peaks with maximum LOD scores of 3.07 and 2.97 were found on chromosomes 7 and 17, respectively. Unexpectedly, we found these siblings to be homozygous for a c.813\_816del (p.Thr272Serfs?10) mutation in the progranulin gene (GRN, granulin precursor) in the latter peak. Heterozygous mutations in GRN are a major cause of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), the second most common early-onset dementia. Reexamination of progranulin-deficient mice revealed rectilinear profiles typical of NCL. The age-at-onset and neuropathology of FTLD-TDP and NCL are markedly different. Our findings reveal an unanticipated link between a rare and a common neurological disorder and illustrate pleiotropic effects of a mutation in the heterozygous or homozygous states.},
          author = {Smith, KR and Damiano, J and Franceschetti, S and Carpenter, S and Canafoglia, L and Morbin, M and Rossi, G and Pareyson, D and Mole, SE and Staropoli, JF and Sims, KB and Lewis, J and Lin, WL and Dickson, DW and Dahl, HH and Bahlo, M and Berkovic, SF},
             url = {http://dx.doi.org/10.1016/j.ajhg.2012.04.021}
}