Abstract

Context

Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of NAFLD, but the mechanism of NAFLD is not completely understood. β-Tubulin is essential in mitoses, neuronal migration, and axon guidance during neuronal development. Pathogenic variants in the TUBB3 gene were shown to be associated with a wide spectrum of neurological abnormalities, but not accompanied by hepatic complications, such as NAFLD.

Objective

This work aims to examine the association between TUBB3 mutation and nonalcoholic steatohepatitis (NASH).

Methods

An 11-year-old girl has been followed up as having atypical Möbius syndrome since infancy, as she was born with bilateral ptosis, paralytic strabismus, and facial weakness. At age 7 years, she was diagnosed with TUBB3 E410K syndrome by whole-exome sequencing. At age 10 years, her blood examination revealed elevated liver transaminase levels, which persisted for almost 2 years. She underwent liver biopsy, the results of which were suggestive of NASH.

Results

The expression of TUBB3 was absent, but that of tyrosine hydroxylase (TH) was present in the parenchymal nerve fibers of the liver. On the other hand, in comparison with an autopsy case of NASH and a normal control, these showed coexpression of TUBB3 and TH in the liver.

Conclusion

We report the first case of TUBB3 E410K syndrome accompanied by NASH. This case suggests that the TUBB3 mutation may be associated with the pathogenesis and progression of NASH in humans.

中文翻译：

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TUBB3 E410K 综合征伴儿童期非酒精性脂肪性肝炎

摘要

语境

非酒精性脂肪性肝病 (NAFLD) 正在成为世界范围内的一个主要问题，甚至在儿童中也是如此。多个平行命中假说已被提出作为 NAFLD 的进展，但 NAFLD 的机制尚不完全清楚。β-微管蛋白在神经元发育过程中对有丝分裂、神经元迁移和轴突引导至关重要。TUBB3基因的致病性变异与广泛的神经系统异常有关，但不伴有肝脏并发症，例如 NAFLD。

客观的

这项工作旨在检查 TUBB3 突变与非酒精性脂肪性肝炎 (NASH) 之间的关联。

方法

一名 11 岁女孩因出生时患有双侧上睑下垂、麻痹性斜视和面部无力，从婴儿期开始就患有非典型莫比乌斯综合征进行了随访。7 岁时，她通过全外显子组测序被诊断出患有TUBB3 E410K 综合征。10 岁时，她的血液检查显示肝转氨酶水平升高，持续了近 2 年。她接受了肝活检，结果提示 NASH。

结果

TUBB3 的表达不存在，但酪氨酸羟化酶（TH）的表达存在于肝脏的实质神经纤维中。另一方面，与 NASH 的尸检病例和正常对照相比，这些显示了 TUBB3 和 TH 在肝脏中的共表达。

结论

我们报告了第一例伴有 NASH的TUBB3 E410K 综合征。该病例提示TUBB3突变可能与人类NASH的发病机制和进展有关。