ScholarLens Back to search
2020•Alzheimer s & DementiaOpen access

Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases

Eliana Marisa Ramos, Deepika Reddy Dokuru, Victoria Van Berlo, Kevin J. Wojta, Qing Wang, Alden Huang, Sandeep Deverasetty, Yue Qin, Marka van Blitterswijk, Jazmyne L. Jackson, Brian Stephen Appleby, Yvette M. Bordelon, Patrick Brannelly, Danielle E. Brushaber, Bradford Clark Dickerson, Susan L.-J. Dickinson, Kimiko Domoto‐Reilly, Kelley M. Faber, Julie A. Fields, Jamie C Fong, Tatiana Foroud, Leah K. Forsberg, Ralitza H. Gavrilova, Nupur Ghoshal, Jill S. Goldman, Jonathan Graff‐Radford, Neill R. Graff‐Radford, Ian M. Grant, Murray Grossman, Hilary W. Heuer, Ging‐Yuek Robin Hsiung, Edward D. Huey, David John Irwin, Kejal Kantarci, Anna Karydas, Daniel Kaufer, Diana R. Kerwin, David S. Knopman, John Kornak, Joel H. Kramer, Walter K. Kremers, Walter A. Kukull, Irene Litvan, Peter Alexander Ljubenkov, Codrin Lungu, Ian R. Mackenzie, Mario F. Mendez, Bruce L. Miller, Chiadi U. Onyike, Alexander Y. Pantelyat, Rodney Pearlman, Len Petrucelli, Madeline Potter, Katherine P. Rankin, Katya Rascovsky, Erik D. Roberson, Emily Joy Rogalski, Leslie M. Shaw, Jeremy A. Syrjanen, Maria Carmela Tartaglia, Nadine A. Tatton, Joanne B. Taylor, Arthur W. Toga, John Q. Trojanowski, Sandra Weıntraub, Bonnie Wong, Zbigniew K. Wszołek, Rosa Rademakers, Bradley F. Boeve, Howard J. Rosen, Adam L. Boxer, Giovanni Coppola

Open full text 83 citations

Abstract

INTRODUCTION: The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes. METHODS: We screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies. RESULTS: Among the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes. DISCUSSION: Our study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

About this research paper

What this paper is about

INTRODUCTION: The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes. METHODS: We screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies. RESULTS: Among the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes. DISCUSSION: Our study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

Why it matters

OpenAlex reports 83 citations for this work. Citation counts describe recorded attention and do not establish research quality.

Key contribution

A contribution statement is not available in the OpenAlex record.

Method / approach

Method details are not available in the OpenAlex metadata.

Main findings

Findings are not separately available in the OpenAlex metadata.

Limitations

Limitations are not available in the OpenAlex metadata.

Applications

Application details are not available in the OpenAlex metadata.

Available abstract

INTRODUCTION: The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes. METHODS: We screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies. RESULTS: Among the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes. DISCUSSION: Our study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

Key concepts: C9orf72, Frontotemporal dementia, TARDBP, Frontotemporal lobar degeneration, Genetics, PSEN1, Medicine, Biology

Related papers

Related paper 1Related paper 2Related paper 3
Back to paper searchBrowse research topicsOriginal source
Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases — Research Paper | ScholarLens