Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis

Abstract

Selective tooth agenesis is the most common developmental abnormality of the human dentition. To date, this abnormality has been associated only with mutations in MSX1 and PAX9 mutations, however it has recently been suggested that mutations of axis inhibition protein 2 (AXIN2) may also contribute to this complex anomaly. The protein product of this gene is a negative regulator of the Wnt-signaling pathway. We searched for AXIN2 variants in a group of patients with tooth agenesis who did not have mutations of MSX1 and PAX9. Using multi-temperature single-stranded conformational polymorphism and sequencing analysis, we identified three novel AXIN2 gene variants: c.956+16A>G, c.1060-17C>T and c.2062C>T. We also observed that individuals carrying the c.956+16G and c.2062T alleles exhibited an increased risk of tooth agenesis. The calculated odds ratio was 2.94 (95% CI 1.104-7.816; p=0.026; p corr =0.234) and 4.01 (95% CI 1.563-10.301; p=0.002; p corr =0.018), respectively. Moreover, we found that the c.2062C>T transition may change exon splice enhancer-specific binding sites of the protein splicing regulators SC35 and SF2/ASF. This alternation may negatively affect the splicing process and cellular concentration of AXIN2 protein. Our findings suggest that AXIN2 polymorphic variants may be associated with both hypodontia and oligodontia.

Association between rs11001553 of DKK1 and non-syndromic tooth agenesis in the Chinese Han population

“…Wnt signaling is essential for tooth development as indicated by transgenic mouse experiments (Mikkola and Millar, 2006). Mutations and polymorphisms in AXIN2, an intracellular antagonist of Wnt signaling, have been associated with tooth agenesis (Lammi et al, 2004;Mostowska et al, 2006;Callahan et al, 2009). WNT10A mutations have also been reported in patients with tooth agenesis (Kantaputra and Sripathomsawat, 2011).…”

“…Previous studies of polymorphisms and tooth agenesis are rare, with most focusing on PAX9, MSX1 and AXIN2 (Mostowska et al, 2006;Bianch et al, 2007;Callahan et al, 2009;Silva et al, 2009). Furthermore, only two studies have focused on the Chinese population (Pan et al, 2008;Liu et al, 2012).…”

A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia

“…The most commonly missing permanent teeth are the third molars (20%), second premolars (3.4%), and maxillary lateral incisors (2.2%) (Simons et al 1993). Four genes underlying isolated or nonsyndromic hypodontia have been identified so far: PAX9 (Stockton et al 2000), MSX1 (Vastardis et al 1996), AXIN2 (Mostowska et al 2006), and EDA (Tao et al 2006). Mutations in the EDA gene are usually associated with syndromic hypodontia involving other ectodermal tissues, but two recent reports indicate that certain EDA mutations may cause isolated hypodontia (Tao et al 2006;Tarpey et al 2007).…”

Süt Ve Dai̇mi̇ Denti̇syonda Görülen Konjeni̇tal Di̇ş Eksi̇kli̇ği̇ Ve Ai̇le İli̇şki̇si̇: 4 Olgu Sunumu

“…Bir başka görüş ise embriyonik mezenkime gelecek herhangi bir zararın diş gelişimini etkileyebileceği teorisidir 11,16 . Yapılan çalışmalarda, hücrelerin birbiri ile etkileşiminde rol alan çeşitli gen ve gen ürünlerinin diş oluşumunda etkili oldukları belirtilmektedir 7,15,17,18 . Genlerin DNA üzerinde yer alan kromozomları etkiledikleri belirtilmektedir.…”