A Novel <scp><i>CHMP2B</i></scp> Splicing Variant in Atypical Presentation of Familial Frontotemporal Lobar Degeneration
C-truncating variants in the charged multivesicular body protein 2B (CHMP2B) gene are a rare cause of frontotemporal lobar degeneration (FTLD), previously identified only in Denmark, Belgium, and China. We report a novel CHMP2B splice-site variant (c.35-1G>A) associated with familial FTLD in Spain. The cases were two monozygotic male twins who presented at ages 62 and 66 years with a slowly progressive behavioral variant of frontotemporal dementia and a syndrome mimicking dementia with Lewy bodies, respectively. Functional and in silico analyses supported the pathogenicity of this variant. Our findings contribute new insights into the genetic landscape and clinical heterogeneity of FTLD.
Authors
- Sara Rubio‐Guerra (ORCID: https://orcid.org/0000-0001-7652-8029)
- Valle Camacho (ORCID: https://orcid.org/0000-0003-0748-0847)
- Juan Fortea (ORCID: https://orcid.org/0000-0002-1340-638X)
- Alberto Lleó (ORCID: https://orcid.org/0000-0002-2568-5478)
- Miguel Santos‐Santos (ORCID: https://orcid.org/0000-0003-1567-617X)
- Ricard Rojas‐García (ORCID: https://orcid.org/0000-0003-1411-5573)
- Isabel Sala (ORCID: https://orcid.org/0000-0002-9886-4792)
- Ignacio Illán‐Gala (ORCID: https://orcid.org/0000-0002-5418-2052)
- J. García Castro (ORCID: https://orcid.org/0000-0003-1503-4775)
- Janina Turón‐Sans (ORCID: https://orcid.org/0000-0002-8842-4646)
- Josefina Pérez‐Blanco
- Oriol Dols‐Icardo (ORCID: https://orcid.org/0000-0003-2656-8748)
- David Almenta (ORCID: https://orcid.org/0000-0001-9069-8948)
- Daniel Andres Alcolea (ORCID: https://orcid.org/0000-0002-3819-3245)
- Álvaro Carbayo (ORCID: https://orcid.org/0000-0001-9282-8603)
- Judit Selma‐González (ORCID: https://orcid.org/0009-0006-1021-4653)
- Sara Bernal (ORCID: https://orcid.org/0000-0003-4427-0574)
- Ma Belén Sánchez‐Saudinós
Institutions
- Universitat Autònoma de Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Hospital de Sant Pau (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
Publication Details
- Journal
- Annals of Clinical and Translational Neurology
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1002/acn3.70023
- Citations
- 1
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- Alzheimer's Association
- BrightFocus Foundation
- Fundación BBVA
- Global Brain Health Institute
- Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica
- Alzheimer Society
- European Commission
- Fondation Jérôme Lejeune
- Generalitat de Catalunya
- Banco Bilbao Vizcaya Argentaria
- Fundación Tatiana Pérez de Guzmán el Bueno
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- National Institutes of Health
- Horizon 2020 Framework Programme
- Instituto de Salud Carlos III
- European Regional Development Fund
- Departament de Salut, Generalitat de Catalunya