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000162928 0247_ $$2doi$$a10.1038/s41380-021-01271-2
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000162928 0247_ $$2ISSN$$a1476-5578
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000162928 037__ $$aDZNE-2021-01580
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000162928 1001_ $$00000-0002-4454-8823$$aWagner, Matias$$b0
000162928 245__ $$aClinico-genetic findings in 509 frontotemporal dementia patients.
000162928 260__ $$aLondon$$bMacmillan$$c2021
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000162928 520__ $$aFrontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. To which extent genetic aberrations dictate clinical presentation remains elusive. We investigated the spectrum of genetic causes and assessed the genotype-driven differences in biomarker profiles, disease severity and clinical manifestation by recruiting 509 FTD patients from different centers of the German FTLD consortium where individuals were clinically assessed including biomarker analysis. Exome sequencing as well as C9orf72 repeat analysis were performed in all patients. These genetic analyses resulted in a diagnostic yield of 18.1%. Pathogenic variants in C9orf72 (n = 47), GRN (n = 26), MAPT (n = 11), TBK1 (n = 5), FUS (n = 1), TARDBP (n = 1), and CTSF (n = 1) were identified across all clinical subtypes of FTD. TBK1-associated FTD was frequent accounting for 5.4% of solved cases. Detection of a homozygous missense variant verified CTSF as an FTD gene. ABCA7 was identified as a candidate gene for monogenic FTD. The distribution of APOE alleles did not differ significantly between FTD patients and the average population. Male sex was weakly associated with clinical manifestation of the behavioral variant of FTD. Age of onset was lowest in MAPT patients. Further, high CSF neurofilament light chain levels were found to be related to GRN-associated FTD. Our study provides large-scale retrospective clinico-genetic data such as on disease manifestation and progression of FTD. These data will be relevant for counseling patients and their families.
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000162928 650_2 $$2MeSH$$aC9orf72 Protein: genetics
000162928 650_2 $$2MeSH$$aFrontotemporal Dementia: genetics
000162928 650_2 $$2MeSH$$aGenotype
000162928 650_2 $$2MeSH$$aHumans
000162928 650_2 $$2MeSH$$aMale
000162928 650_2 $$2MeSH$$aMutation
000162928 650_2 $$2MeSH$$aRetrospective Studies
000162928 650_2 $$2MeSH$$aExome Sequencing
000162928 650_2 $$2MeSH$$atau Proteins: genetics
000162928 7001_ $$aLorenz, Georg$$b1
000162928 7001_ $$aVolk, Alexander E$$b2
000162928 7001_ $$00000-0002-5183-780X$$aBrunet, Theresa$$b3
000162928 7001_ $$0P:(DE-2719)2231621$$aEdbauer, Dieter$$b4$$udzne
000162928 7001_ $$00000-0003-1862-3700$$aBerutti, Riccardo$$b5
000162928 7001_ $$aZhao, Chen$$b6
000162928 7001_ $$aAnderl-Straub, Sarah$$b7
000162928 7001_ $$00000-0002-0108-124X$$aBertram, Lars$$b8
000162928 7001_ $$0P:(DE-2719)2810712$$aDanek, Adrian$$b9$$udzne
000162928 7001_ $$aDeschauer, Marcus$$b10
000162928 7001_ $$00000-0002-4258-4986$$aDill, Veronika$$b11
000162928 7001_ $$00000-0003-3596-868X$$aFassbender, Klaus$$b12
000162928 7001_ $$0P:(DE-2719)2811326$$aFliessbach, Klaus$$b13$$udzne
000162928 7001_ $$aGötze, Katharina S$$b14
000162928 7001_ $$aJahn, Holger$$b15
000162928 7001_ $$00000-0002-8096-3987$$aKornhuber, Johannes$$b16
000162928 7001_ $$aLandwehrmeyer, Bernhard$$b17
000162928 7001_ $$aLauer, Martin$$b18
000162928 7001_ $$aObrig, Hellmuth$$b19
000162928 7001_ $$0P:(DE-2719)2380559$$aPrudlo, Johannes$$b20$$udzne
000162928 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b21$$udzne
000162928 7001_ $$aSchroeter, Matthias L$$b22
000162928 7001_ $$aUttner, Ingo$$b23
000162928 7001_ $$0P:(DE-2719)9001493$$aVukovich, Ruth C.$$b24$$udzne
000162928 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b25$$udzne
000162928 7001_ $$aWinkler, Andrea S$$b26
000162928 7001_ $$0P:(DE-2719)2811347$$aZhou, Qihui$$b27$$udzne
000162928 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert C$$b28$$udzne
000162928 7001_ $$aconsortium, German FTLD$$b29$$eCollaboration Author
000162928 7001_ $$aOexle, Konrad$$b30
000162928 7001_ $$00000-0003-4273-4267$$aOtto, Markus$$b31
000162928 7001_ $$0P:(DE-2719)2811585$$aDiehl-Schmid, Janine$$b32$$udzne
000162928 7001_ $$00000-0002-3074-599X$$aWinkelmann, Juliane$$b33$$eCorresponding author
000162928 773__ $$0PERI:(DE-600)1502531-7$$a10.1038/s41380-021-01271-2$$n10$$p5824-5832$$tMolecular psychiatry$$v26$$x1476-5578$$y2021
000162928 8564_ $$uhttps://www.nature.com/articles/s41380-021-01271-2
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