The heritability and genetics of frontotemporal lobar degeneration. Export

@article{citeulike:6057509, abstract = {BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder. METHODS: We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease. RESULTS: A total of 41.8\% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2\% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9\% of the cohort) and GRN (8.4\%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups: type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1). CONCLUSION: These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation.}, author = {Rohrer, J. D. and Guerreiro, R. and Vandrovcova, J. and Uphill, J. and Reiman, D. and Beck, J. and Isaacs, A. M. and Authier, A. and Ferrari, R. and Fox, N. C. and Mackenzie, I. R. and Warren, J. D. and de Silva, R. and Holton, J. and Revesz, T. and Hardy, J. and Mead, S. and Rossor, M. N.}, citeulike-article-id = {6057509}, citeulike-linkout-0 = {http://dx.doi.org/10.1212/WNL.0b013e3181bf997a}, citeulike-linkout-1 = {http://www.neurology.org/content/73/18/1451.abstract}, citeulike-linkout-2 = {http://www.neurology.org/content/73/18/1451.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19884572}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19884572}, day = {3}, doi = {10.1212/WNL.0b013e3181bf997a}, issn = {1526-632X}, journal = {Neurology}, keywords = {frontotemporal\_dementia, frontotemporal\_lobar\_degeneration, genetics, mapt, pgrn, tau}, month = {November}, number = {18}, pages = {1451--1456}, posted-at = {2009-11-04 22:52:28}, priority = {3}, title = {The heritability and genetics of frontotemporal lobar degeneration.}, url = {http://dx.doi.org/10.1212/WNL.0b013e3181bf997a}, volume = {73}, year = {2009} }

TY - JOUR ID - citeulike:6057509 L3 - citeulike-article-id:6057509 N2 - BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder. METHODS: We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease. RESULTS: A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9% of the cohort) and GRN (8.4%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups: type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1). CONCLUSION: These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation. IS - 18 JF - Neurology SN - 1526-632X EP - 1456 TI - The heritability and genetics of frontotemporal lobar degeneration. VL - 73 SP - 1451 KW - frontotemporal_dementia KW - frontotemporal_lobar_degeneration KW - genetics KW - mapt KW - pgrn KW - tau AU - Rohrer, JD AU - Guerreiro, R AU - Vandrovcova, J AU - Uphill, J AU - Reiman, D AU - Beck, J AU - Isaacs, AM AU - Authier, A AU - Ferrari, R AU - Fox, NC AU - Mackenzie, IR AU - Warren, JD AU - de Silva, R AU - Holton, J AU - Revesz, T AU - Hardy, J AU - Mead, S AU - Rossor, MN PY - 2009/11/03/ UR - http://dx.doi.org/10.1212/WNL.0b013e3181bf997a ER -