eprintid: 10206045
rev_number: 9
eprint_status: archive
userid: 699
dir: disk0/10/20/60/45
datestamp: 2025-03-13 10:13:49
lastmod: 2025-03-13 10:13:49
status_changed: 2025-03-13 10:13:49
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Aynekin, Busra
creators_name: Akbaş, Sinan
creators_name: Gulec, Ayten
creators_name: Gumus, Ummu Gulsum Ozgul
creators_name: Guner, Abdullah Emre
creators_name: Efthymiou, Stephanie
creators_name: Houlden, Henry
creators_name: Sayin, Gözde Yesil
creators_name: Per, Huseyin
title: Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F85
keywords: Microtubule; PEBAT; WES; 
Neurodevelopmental disorder
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder. We report three cases from two consanguineous families with varying clinical presentations of PEBAT syndrome due to homozygous pathogenic variants in the TBCD. In Family 1, two siblings (F1C1 and F1C2) harboring the homozygous c.2314C > T, p.(Arg772Cys) variant exhibited severe neurodevelopmental regression, spastic tetraplegia, seizures, and brain atrophy. In contrast, Family 2, Case 3 (F2C3), with the homozygous c.230A > G, p.(His77Arg) variant, presented a milder phenotype, including absence seizures, slight developmental delay, and less pronounced neuroanatomical abnormalities. These findings contribute to the expanding phenotypic spectrum of PEBAT and suggesting that modifier genes or epigenetic factors may influence disease severity.
date: 2025-01-24
date_type: published
publisher: Springer Verlag
official_url: https://doi.org/10.1007/s10048-025-00799-7
full_text_type: other
language: eng
verified: verified_manual
elements_id: 2358430
doi: 10.1007/s10048-025-00799-7
medium: Electronic
pii: 10.1007/s10048-025-00799-7
lyricists_name: Houlden, Henry
lyricists_name: Efthymiou, Stephanie
lyricists_id: HJHOU44
lyricists_id: SEFTH99
actors_name: Efthymiou, Stephanie
actors_id: SEFTH99
actors_role: owner
funding_acknowledgements: [Wellcome Trust]; [MRC]; [MSA Trust]; [National Institute for Health Research University College London Hospitals Biomedical Research Centre NIHR-BRC]; [Michael J Fox Foundation (MJFF)]; [Rosetrees Trust]; [Dolby Family fund]; [Alzheimer's Research UK (ARUK)]; [MSA Coalition, Parkinson's disease society, Parkinson's Foundation]; [Fidelity Trust]; [Guarantors of Brain, Cerebral Palsy Alliance]; [Victoria Brain bank]; [NIH NeuroBioBank]; [Queen Square BrainBank,]; [MRC Brainbank Network]; [FARA]; [EAN]
full_text_status: restricted
publication: Neurogenetics
volume: 26
article_number: 23
pages: 8
event_location: United States
issn: 1364-6745
citation:        Aynekin, Busra;    Akbaş, Sinan;    Gulec, Ayten;    Gumus, Ummu Gulsum Ozgul;    Guner, Abdullah Emre;    Efthymiou, Stephanie;    Houlden, Henry;         ... Per, Huseyin; + view all <#>        Aynekin, Busra;  Akbaş, Sinan;  Gulec, Ayten;  Gumus, Ummu Gulsum Ozgul;  Guner, Abdullah Emre;  Efthymiou, Stephanie;  Houlden, Henry;  Sayin, Gözde Yesil;  Per, Huseyin;   - view fewer <#>    (2025)    Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.                   Neurogenetics , 26     , Article 23.  10.1007/s10048-025-00799-7 <https://doi.org/10.1007/s10048-025-00799-7>.      
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10206045/1/Efthymiou_30%20December%20TBCD%20Manuscript.pdf