Background

Severe loss of TBCE function has been related to two well-known dysmorphic syndromes, while TBCE hypomorphic variants have been linked to neurodegenerative conditions due to perturbed microtubule dynamics and homeostasis, with signs of central and peripheral nervous system involvement.

Method

We report on an Italian female originating from Southern Italy who presented early-onset regression and neurodegeneration, with neurological features of tetraparesis and signs of peripheral nervous system involvement. Her brain MRI revealed white matter involvement.

Results

Analyzing all known hypomyelination leukodystrophies related genes, two mutations in TBCE (NM_001079515) were detected: the missense variant c.464 T > A; p. (Ile155Asn) and the frameshift variant c.924del; p. (Leu309Ter), in compound heterozygosity, already reported in the literature in patients coming from the same geographical area. The clinical phenotype of the proposita was more severe and with an earlier onset than the majority of the patients reported so far.

Conclusions

Next Generation Sequencing is becoming increasingly necessary to assess unusual phenotypes, with the opportunity to establish prognosis and disease mechanisms, and facilitating differential diagnosis.

中文翻译：

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拓宽 TBCE 相关神经元神经变性的谱表型

背景

TBCE 功能的严重丧失与两种众所周知的畸形综合征有关，而TBCE亚形态变异与由于微管动力学和稳态受扰动的神经退行性疾病有关，并伴有中枢和周围神经系统受累的迹象。

方法

我们报告了一名来自意大利南部的意大利女性，她表现出早发性退化和神经退行性变，具有四肢轻瘫的神经学特征和周围神经系统受累的迹象。她的脑部 MRI 显示白质受累。

结果

分析所有已知的低髓鞘化脑白质营养不良相关基因，检测到TBCE (NM_001079515) 中的两个突变：错义变异 c.464 T > A；页。(Ile155Asn) 和移码变体 c.924de​​l；页。(Leu309Ter)，复合杂合性，已经在文献中报道了来自同一地理区域的患者。与迄今为止报告的大多数患者相比，proposita 的临床表型更严重且发病更早。

结论

下一代测序对于评估异常表型变得越来越必要，有机会建立预后和疾病机制，并促进鉴别诊断。