Dental Research Center, Tehran University of Medical Science, Tehran, Iran.
Oral & Maxillofacial Medicine Department, School of Dentistry, Tehran University of Medical Science, Tehran, Iran.
Clin Oral Investig. 2024 Jul 18;28(8):432. doi: 10.1007/s00784-024-05819-8.
Temporomandibular joint disorder (TMD) is a complex condition with pain and dysfunction in the temporomandibular joint and related muscles. Scientific evidence indicates both genetic and environmental factors play a crucial role in TMD. In this study, we aimed to discover the genetic changes in individuals from 4 generations of an Iranian family with signs and symptoms of TMD and malocclusion Class III.
Whole Exome Sequencing (WES) was performed in 4 patients (IV-8, IV-9, V-4, and V-6) with TMD according to (DC/TMD), along with skeletal Class III malocclusion. Then, PCR sequencing was performed on 23 family members to confirm the WES.
In the present study, WES results analysis detected 6 heterozygous non-synonymous Single Nucleotide Variants (SNVs) in 5 genes, including CRLF3, DNAH17, DOCK1, SEPT9, and VWDE. A heterozygous variant, c.2012T > A (p.F671Y), in Exon 20 of the DOCK1 (NM_001290223.2) gene was identified. Then, this variant was investigated in 19 other members of the same family. PCR-Sequencing results showed that 7/19 had heterozygous TA genotype, all of whom were accompanied by malocclusion and TMD symptoms and 12/19 individuals had homozygous TT genotype, 9 of whom had no temporomandibular joint problems or malocclusion. The remaining 3 showed mild TMD clinical symptoms. The 5 other non-synonymous SNVs of CRLF3, DNAH17, SEPT9, and VWDE were not considered plausible candidates for TMD.
The present study identified a heterozygous nonsynonymous c.2012T > A (p.F671Y) variant of the DOCK1 gene is significantly associated with skeletal class III malocclusion, TMD, and its severity in affected individuals in the Iranian pedigree.
The role of genetic factors in the development of TMD has been described. The present study identified a nonsynonymous variant of the DOCK1 gene as a candidate for TMD and skeletal class III malocclusion in affected individuals in the Iranian pedigree.
颞下颌关节紊乱（TMD）是一种复杂的疾病，表现为颞下颌关节及其相关肌肉疼痛和功能障碍。科学证据表明，遗传和环境因素都在 TMD 中起着至关重要的作用。在这项研究中，我们旨在发现一个伊朗家族的 4 代人中有 TMD 和 III 类错颌畸形的个体的遗传变化。
根据（DC/TMD）对 4 名 TMD 患者（IV-8、IV-9、V-4 和 V-6）进行全外显子组测序（WES），同时伴有骨骼 III 类错颌畸形。然后，对 23 名家族成员进行 PCR 测序以确认 WES。
在本研究中，WES 结果分析在 5 个基因中检测到 6 个杂合非同义单核苷酸变异（SNVs），包括 CRLF3、DNAH17、DOCK1、SEPT9 和 VWDE。在 DOCK1（NM_001290223.2）基因的外显子 20 中发现了一个杂合变异 c.2012T > A（p.F671Y）。然后，在同一家庭的其他 19 名成员中对该变异进行了研究。PCR 测序结果显示，7/19 具有杂合 TA 基因型，均伴有错颌畸形和 TMD 症状，12/19 个体具有纯合 TT 基因型，其中 9 人无颞下颌关节问题或错颌畸形。其余 3 人表现出轻度 TMD 临床症状。CRLF3、DNAH17、SEPT9 和 VWDE 的其他 5 个非同义 SNVs 不被认为是 TMD 的合理候选者。
本研究发现，DOCK1 基因的杂合非同义 c.2012T > A（p.F671Y）变异与伊朗家系中受累个体的骨骼 III 类错颌畸形、TMD 及其严重程度显著相关。
遗传因素在 TMD 的发生发展中的作用已被描述。本研究在伊朗家系中受累个体中发现了 DOCK1 基因的非同义变异是 TMD 和骨骼 III 类错颌畸形的候选基因。
