Missense variants in TUBB3 have historically been associated with either congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or malformations of cortical development (MCD). Until a recent report identified two amino acid substitutions in four patients that had clinical features of both disorders, pathogenic variants of TUBB3 were thought distinct to either respective disorder. Three recurrent de novo Gly71Arg TUBB3 substitutions and a single patient with a de novo Gly98Ser substitution blurred the MCD and CFEOM3 phenotypic distinctions. Here we report a second patient with a missense c.292G>A (p.Gly98Ser) substitution, but without CFEOM3, the first reported evidence that even the same TUBB3 substitution can produce a spectrum of TUBB3 syndrome phenotypes. Our patient presented with amblyopia, exotropia, optic disc pallor, and developmental delay. Neuroimaging identified hypoplasia of the corpus callosum, interdigitation of the frontal lobe gyri, and dysplasia or hypoplasia of the optic nerves, basal ganglia, brainstem, and cerebellum. This report identifies the TUBB3 Gly98Ser substitution to be recurrent but inconsistently including CFEOM3, and identifies the absence of joint contractures and the presence of optic disc abnormalities that may be genotype‐specific to the TUBB3 Gly98Ser substitution.

中文翻译：

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TUBB3 Gly98Ser的经常性替代是第一个被描述为不一致地导致CFEOM3的突变。

TUBB3中的错义变体历史上与3型眼外肌先天性纤维化（CFEOM3）或皮质发育畸形（MCD）相关。直到最近的报告在四名具有两种疾病的临床特征的患者中鉴定出两个氨基酸取代之前，TUBB3的致病变体才被认为与两种疾病均不同。三份经常从头Gly71Arg TUBB3替换和一个病人用从头Gly98Ser替代模糊了MCD和CFEOM3表型的区别。在这里，我们报告第二例患者出现了错义的c.292G> A（p.Gly98Ser）替代，但没有CFEOM3，第一个报告的证据表明，即使相同的TUBB3替代也可以产生TUBB3光谱综合征表型。我们的患者出现弱视，散光，视盘苍白和发育迟缓。神经影像学检查发现identified体发育不全，额叶回旋指叉，视神经，基底神经节，脑干和小脑发育异常或发育不全。该报告确定了TUBB3 Gly98Ser置换是复发性的，但包括CFEOM3却不一致，并且确定了关节挛缩的缺失和视盘异常的存在，这些异常可能是TUBB3 Gly98Ser置换的基因型特异性的。