目的:颞下颌关节紊乱病(TMD)是一种复杂的疾病,伴有颞下颌关节及相关肌肉的疼痛和功能障碍。科学证据表明,遗传和环境因素在TMD中起着至关重要的作用。在这项研究中,我们的目的是发现一个伊朗家族4代有TMD和III类错牙合体征和症状的个体的遗传变化。
方法:根据(DC/TMD)对4例TMD患者(IV-8,IV-9,V-4和V-6)进行了全外显子组测序(WES),伴随着骨骼III类错牙合。然后,对23个家族成员进行PCR测序以确认WES。
结果: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体(SNV),包括CRLF3、DNAH17、DOCK1、SEPT9和VWDE。杂合变体,c.2012T>A(p。F671Y),在DOCK1(NM_001290223.2)基因的外显子20中鉴定。然后,在同一家族的其他19名成员中对该变异进行了调查.PCR-测序结果显示7/19具有杂合子TA基因型,所有患者均伴有错牙合畸形和TMD症状,12/19个体具有纯合TT基因型,其中9人没有颞下颌关节问题或错牙合。其余3例表现为轻度TMD临床症状。CRLF3,DNAH17,SEPT9和VWDE的其他5种非同义SNV被认为不是TMD的合理候选者。
结论:本研究确定了一个杂合的非同义c.2012T>A(p。DOCK1基因的F671Y)变体与骨骼III类错牙合显著相关,TMD,以及它在伊朗血统中受影响的个体中的严重程度。
结论:已经描述了遗传因素在TMD发展中的作用。本研究确定了DOCK1基因的非同义变体,可作为伊朗谱系中受影响个体的TMD和骨骼III类错合的候选者。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.