TY  - JOUR
JF  - Neurogenetics
A1  - Aynekin, Busra
A1  - Akba?, Sinan
A1  - Gulec, Ayten
A1  - Gumus, Ummu Gulsum Ozgul
A1  - Guner, Abdullah Emre
A1  - Efthymiou, Stephanie
A1  - Houlden, Henry
A1  - Sayin, Gözde Yesil
A1  - Per, Huseyin
KW  - Microtubule; PEBAT; WES; 
Neurodevelopmental disorder
N2  - 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 ?/?-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.
ID  - discovery10206045
PB  - Springer Verlag
UR  - https://doi.org/10.1007/s10048-025-00799-7
SN  - 1364-6745
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
TI  - Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families
Y1  - 2025/01/24/
AV  - restricted
VL  - 26
EP  - 8
ER  -