The First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan.
J Dent Res. 2012 Jul;91(7 Suppl):38S-44S. doi: 10.1177/0022034512447952.
Oculodentodigital Dysplasia (ODDD) is a rare syndrome involving anomalies in eye, tooth, and digit formation, caused by mutations in CX43/GJA1. In addition to classic dental features, ODDD includes oral and craniofacial accessory symptoms such as characteristic facial appearance and cleft palate. However, there have been no reports of ODDD accompanied by cleft lip. Herein we report, for the first time, a male, sporadic, Asian proband presenting bilateral cleft lip. By direct sequence analysis, our proband was diagnosed as having ODDD with a heterozygous mutation, codon 142 G>A in GJA1 and CX43E48K. We excluded the possibility of pathogenic mutations in B3GALTL, BMP4, TFAP2A, PVRL1, IRF6, and MSX1. To address how CX43/GJA1 is related to cleft lip, we performed immunohistochemistry using mouse and human mid-facial tissue. CX43 expression was detected in the nasal compartment and nasal and maxillary processes at murine developmental stage E12.5. Furthermore, CX43 expression was found in the epithelial tissue inside the human subepithelial cleft lip that completes epithelial fusion. Therefore, we suggest that CX43/GJA1 is involved in lip formation. Our case report of ODDD with a bilateral cleft lip suggests that CX43/GJA1 might be a novel candidate gene for syndromic cleft lip.
眼牙指发育不良（ODDD）是一种罕见的综合征，涉及眼睛、牙齿和手指的形成异常，由 CX43/GJA1 基因突变引起。除了典型的牙齿特征外，ODDD 还包括口腔和颅面附属症状，如特征性面部外观和腭裂。然而，目前还没有 ODDD 伴唇裂的报道。在此，我们首次报道了一名男性、散发性、亚洲先证者，表现为双侧唇裂。通过直接序列分析，我们的先证者被诊断为 ODDD，存在 GJA1 和 CX43E48K 的杂合突变，密码子 142 G>A。我们排除了 B3GALTL、BMP4、TFAP2A、PVRL1、IRF6 和 MSX1 中致病性突变的可能性。为了解 CX43/GJA1 与唇裂的关系，我们使用鼠和人面部组织进行了免疫组织化学染色。在鼠发育阶段 E12.5 时，在鼻区和鼻上颌突中检测到 CX43 的表达。此外，在完成上皮融合的人亚上皮唇裂的上皮组织中也发现了 CX43 的表达。因此，我们认为 CX43/GJA1 参与了唇的形成。我们的 ODDD 伴双侧唇裂病例报告表明，CX43/GJA1 可能是综合征性唇裂的一个新候选基因。
