Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs.

胼胝体异常（CCA）是一种常见的先天性脑异常，病因多样。尽管最重要的病因之一是遗传因素，但 CCA 的遗传背景是异质的，多种类型的变异可能是致病因素。在这项研究中，我们分析了 16 名日本胼胝体异常患者，以描述 CCA 的临床特征和遗传背景。我们观察到伴随 CCA 的常见表型：智力障碍 (100%)、运动发育迟缓 (93.8%)、癫痫发作 (60%) 和面部畸形 (50%)。脑磁共振成像显示阴道头畸形（侧脑室后角扩大，84.6%）和小脑上池扩大（41.7%）。全外显子组测序揭示了 16 名患者中有 9 名（56.3%）的基因改变，ARID1B、CDK8、HIVEP2和TCF4 ）和TBCK的隐性变体。在三个不相关的个​​体中发现了新的 ARID1B 变体，这表明 ARID1B变体是CCA 的主要遗传原因。包含TCF4的 18q21.31-qter 的从头TCF4变体和体细胞镶嵌缺失表明TCF4异常与 CCA 相关。这项使用全外显子组测序分析 CCA 患者的研究表明，综合遗传分析将有助于研究 CCA 的各种因果变异。