Cao, Lauren Y;
Duemler, Anna;
Jung, Emily H;
Maldonado, Ramiro S;
Richards, Sarah;
Schiff, Elena R;
Mahroo, Omar A;
... Alekseev, Oleg; + view all
(2025)
A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss.
Ophthalmic Genetics
10.1080/13816810.2025.2565651.
(In press).
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Abstract
INTRODUCTION: Pathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot. METHODS: Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing. RESULTS: We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot. DISCUSSION: This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.
| Type: | Article |
|---|---|
| Title: | A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/13816810.2025.2565651 |
| Publisher version: | https://doi.org/10.1080/13816810.2025.2565651 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. |
| Keywords: | LCAEOD, TUBB4B, cone-rod dystrophy, β-tubulin 4B |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215523 |
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