Heterozygous variants in TUBB encoding one of β-tubulin isotypes are known to cause two overlapping developmental brain disorders, complex cortical dysplasia with other brain malformations (CDCBM) and congenital symmetric circumferential skin creases (CSCSC). To date, six cases of CSCSC and eight cases of CDCBM caused by nine heterozygous variants have been reported. Here we report two cases with novel de novo missense TUBB variants (NM_178014.4:c.863A>G, p.(Glu288Gly) and c.869C>T, p.(Thr290Ile)). Case 1 presented brain malformations consistent with tubulinopathies including abnormalities in cortex, basal ganglia, corpus callosum, brain stem, and cerebellum along with other systemic features such as coloboma, facial dysmorphisms, vesicoureteral reflux, hypoplastic kidney, and cutis laxa-like mild skin loosening. Another case presented abnormalities of the corpus callosum, brain stem, and cerebellum along with facial dysmorphisms. We reviewed previous literature and suggest the diversity of clinical findings of TUBB-related disorders.

已知 TUBB中编码一种 β-微管蛋白同种型的杂合变体会导致两种重叠的发育性脑疾病，复杂的皮质发育不良伴其他脑畸形 (CDCBM) 和先天性对称圆周皮肤皱褶 (CSCSC) 。迄今为止，已报道了由九个杂合变异引起的六例CSCSC和八例CDCBM。在这里，我们报告了两个新的从头错义TUBB的案例变体（NM_178014.4:c.863A>G, p.(Glu288Gly) 和 c.869C>T, p.(Thr290Ile)）。病例 1 呈现与肾小管病变一致的脑畸形，包括皮质、基底节、胼胝体、脑干和小脑异常以及其他全身特征，如缺损、面部畸形、膀胱输尿管反流、肾发育不全和皮肤松弛样轻度皮肤松弛. 另一例出现胼胝体、脑干和小脑异常以及面部畸形。我们回顾了以前的文献，并提出了TUBB相关疾病的临床发现的多样性。