Plastic and Reconstructive Surgery Unit, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Princess Sirindhorn IT Foundation Craniofacial Center, Chiang Mai University, Chiang Mai, 50200, Thailand.
Sci Rep. 2024 Sep 29;14(1):22555. doi: 10.1038/s41598-024-74353-0.
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial anomalies. Abnormal Alu methylation in DNA of the pregnant mother may influence the abnormal development of the child. This study aimed to examine Alu methylation and cellular senescence in NSCL/P patients and their mothers as well as the correlation with the severity of NSCL/P. A total of 39 patients with NSCL/P and 33 mothers were enrolled. Of these patients, 6 were cleft lip only (CLO), 9 were cleft palate only (CPO), and 24 were cleft lip and palate (CLP). Alu methylation and senescence markers were determined in the white blood cells of NSCL/P patients, their mothers, and in the lip and palatal tissues of patients at the time of cheiloplasty and palatoplasty. Total Alu methylation was not significantly different between groups. However, a decrease in Alu hypermethylation, increased partial Alu methylation, RAGE, and p16 expression were shown in CLP, the most severe cleft type. Alu methylation in tissues did not differ between groups. In mothers, an increase in Alu methylation was observed only in the CLP. Therefore, the pathogenesis of NSCL/P may be related to Alu methylation of the mother promoting loss of Alu methylation and subsequently senescence in the children.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是最常见的颅面畸形之一。孕妇 DNA 中的异常 Alu 甲基化可能会影响孩子的异常发育。本研究旨在检测 NSCL/P 患者及其母亲的 Alu 甲基化和细胞衰老情况，以及与 NSCL/P 严重程度的相关性。共纳入 39 名 NSCL/P 患者和 33 名母亲。其中 6 名为单纯唇裂（CLO），9 名为单纯腭裂（CPO），24 名为唇腭裂（CLP）。在唇腭裂修复术时，测定了 NSCL/P 患者及其母亲的白细胞、唇腭裂组织中的 Alu 甲基化和衰老标志物。各组间总 Alu 甲基化无显著差异。然而，CLP 患者（最严重的腭裂类型）表现为 Alu 超甲基化减少、部分 Alu 甲基化增加、RAGE 和 p16 表达增加。各组间组织中的 Alu 甲基化无差异。仅在 CLP 母亲中观察到 Alu 甲基化增加。因此，NSCL/P 的发病机制可能与母亲的 Alu 甲基化促进 Alu 甲基化丢失和随后的儿童衰老有关。
