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Genetic Change Investigation in Dock1 Gene in an Iranian Family With Sign and Symptoms of Temporomandibular Joint Disorder (Tmd) Publisher Pubmed



Najafi S1, 2 ; Hashemigorji F4 ; Roudgari H4 ; Goudarzi M2 ; Jafarzadegan AM2 ; Sheykhbahaei N2
Authors
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Authors Affiliations
  1. 1. Dental Research Center, Tehran University of Medical Science, Tehran, Iran
  2. 2. Oral & amp
  3. 3. Maxillofacial Medicine Department, School of Dentistry, Tehran University of Medical Science, Tehran, Iran
  4. 4. Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Laser Research Center of Dentistry, Dentistry Research Institute, Tehran University of Medical Science, Tehran, Iran
  6. 6. Oral and maxillofacial pain fellowship, Department of Oral and Maxillofacial Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Clinical Oral Investigations Published:2024


Abstract

Objectives: 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. Materials and 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. Clinical relevance: 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. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
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