典型热点外的一种新的错义TUBB4B变体与锥杆营养不良和感音神经性听力损失有关。

IF 1 4区 医学 Q4 GENETICS & HEREDITY
Lauren Y Cao, Anna Duemler, Emily H Jung, Ramiro S Maldonado, Sarah Richards, Elena R Schiff, Omar A Mahroo, Andrew R Webster, Siying Lin, Beau J Fenner, Alessandro Iannaccone, Oleg Alekseev
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引用次数: 0

摘要

TUBB4B的致病变异编码微管亚基β-微管蛋白4B同型,与Leber先天性黑蒙伴早发性耳聋(LCAEOD)有关,LCAEOD是一种常染色体显性遗传病,以早期和严重的光感受器和耳蜗细胞丧失为特征。大多数报告的病例以早期发病为特征,是由R390/R391热点的错义突变引起的。方法:多模式评估包括超宽视场假彩色和自体荧光眼底摄影、光谱域光学相干断层扫描、全视场视网膜电图、Goldmann动力学视野、听力学和下一代测序基因检测。结果:我们报告了来自三个不相关家族的7名患者,他们患有与TUBB4B基因新变异相关的锥杆营养不良和感音神经性听力损失(c.784C . > T, p.R262W)。与典型热点变异引起的Leber先天性黑朦相比,与这种变异相关的锥杆营养不良通常具有发病年龄较晚的特点。讨论:本报告扩展了R390/R391热点之外的tubb4b相关视网膜病变的突变谱和表型范围,并可能为这种罕见的小管病变的发病机制提供见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss.

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.

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来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
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