A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia.
Bottom Line: Brain imaging from available cases showed a symmetrical pattern of atrophy particularly affecting the frontal and temporal lobes.Pathologically two cases were classified as FTLD-TDP type A with TDP-43 positive inclusions, with additional p62-positive 'star-like' inclusions found in the hippocampal formation and cerebellum.However the driving force of the pathological process may be either pathogenic mutation or a combination of both converging on a singular mechanism.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.Show MeSH
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Mentions: rpPCR assessment of C9orf72 hexonucleotide number demonstrated a minimum of 67 repeats in DNA from both patients on one allele and 2 repeats on the other allele. The presence of a large expansion was confirmed by Southern blotting (Figure 3) which revealed a maximum repeat number in the DNA from brain from case 2.2 (PDG1083) as 4153 repeats, minimum 1205 (modals measured at 3822, 2500 and 2050 repeats), and in DNA from peripheral lymphocytes from case 2.1 (PDG 3296) a maximum of 3316 was measured and minimum of 812 (modal 2780). Genotyping of rs3849942 demonstrated heterozygosity at this polymorphic site for both patients.
Affiliation: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.