Mutations in the osteoprotegerin-encoding gene are associated with temporomandibular joint ankylosis.

Objective: This study aimed to investigate genetic variations in the osteoprotegerin-encoding gene (TNFRSF11B) in patients with temporomandibular joint ankylosis (TMJA).

Study Design: The sample comprised 17 patients diagnosed with TMJA, of both sexes with ages ranging from 6 to 57 years old. TNFRSF11B mutational analysis was performed using the Sanger sequencing method with DNA extracted from oral cells, and the functional impact prediction of the variants was assessed using bioinformatic analysis.

Results: Sequencing analysis identified 15 (88.23%) patients that presented at least 1 genetic variant in TNFRSF11B. The mutation rs202090603 (p.E33K) was found in 6 individuals, and rs140782326 (p.V281M), rs11573942 (p.L295), and rs1375250340 (p.I389T) were identified in 1 subject each. According to the pathogenicity potential of mutations, 3 variants were considered of low impact (rs2073618, rs202090603, and rs2228568) and 3 as disease causing (rs140782326, rs11573942, and rs1375250340). The variant rs202090603 (p.E33K) was found in the first cysteine domain with differences in the loop positions of p.E33K mutated the 3D structure of osteoprotegerin.

Conclusion: Two polymorphisms (rs2073618 and rs2228568) and the mutations rs202090603 (p.E33K), rs140782326 (p.V281M), rs11573942 (p.L295), and rs1375250340 (p.I389T) in the TNFRSF11B gene may be associated with TMJA.