FREM2 is a member of the FREM2–FRAS1–FREM1 protein complex which contributes to epithelial–mesenchymal coupling. We report a Thai woman with cryptophthalmos, dental anomalies, and oral vestibule defect. A compound heterozygous mutation (c.6499C>T; p.Arg2167Trp and c.641_642del; p.Glu214GlyfsTer135) in the FREM2 gene was identified. The frameshift variant p.Glu214GlyfsTer135 is de novo and novel. It is predicted to result in the loss of most of the functional domains. The p.Arg2167Trp mutation was predicted to disrupt both Ca²⁺ binding and conformational change. The Arg2167Trp mutant protein has been shown to cause partial loss of function, decrease its interaction with FREM1 and result in impaired function of the FRAS1–FREM2–FREM1 complex. Frem2 was shown to be expressed in the developing tooth and vestibular lamina. It is hypothesized that these mutations resulted in aberration of the FRAS1–FREM2–FREM1 protein complex, resulting in loss of nephronectin, basement membrane disruption, and abnormal epithelial–mesenchymal interactions leading to dental and oral vestibule malformations.

FREM2 是 FREM2-FRAS1-FREM1 蛋白复合物的成员，有助于上皮-间质偶联。我们报告一名患有隐眼、牙齿异常和口腔前庭缺陷的泰国女性。鉴定了FREM2基因中的复合杂合突变（c.6499C>T；p.Arg2167Trp 和 c.641_642del；p.Glu214GlyfsTer135） 。移码变体 p.Glu214GlyfsTer135 是从头和新颖的。预计会导致大部分功能域的丢失。预计 p.Arg2167Trp 突变会破坏 Ca ²⁺结合和构象变化。Arg2167Trp 突变蛋白已被证明会导致部分功能丧失，减少其与 FREM1 的相互作用并导致 FRAS1-FREM2-FREM1 复合物的功能受损。频率2显示在发育中的牙齿和前庭椎板中表达。据推测，这些突变导致 FRAS1-FREM2-FREM1 蛋白复合物的异常，导致肾连接素丢失、基底膜破坏和异常上皮-间质相互作用导致牙齿和口腔前庭畸形。