TBX22 mutations are a frequent cause of non‐syndromic cleft palate in the Thai population

Abstract

Mutations in the TBX22 gene underlie an X-linked malformation syndrome with cleft palate (CP) and ankyloglossia. Its mutations also result in non-syndromic CP in some populations. To investigate whether mutations in TBX22 play a part in the formation of non-syndromic CP in the Thai population, we performed mutation analysis covering all the coding regions of the TBX22 gene in 53 unrelated Thai patients with non-syndromic CP. We identified four potentially pathogenic mutations, 359G-->A (R120Q), 452G-->T (R151L), 1166C-->A (P389Q), and 1252delG in four different patients. All mutations were not detected in at least 112 unaffected ethnic-matched control chromosomes and had never been previously reported. R120Q and R151L, found in two sporadic cases, were located in the DNA binding T-box domain. P389Q and 1252delG, found in two familial cases, were at the carboxy-terminal region, which has never been described. Our study indicates that TBX22 mutations are responsible for a significant proportion of Thai non-syndromic CP cases confirming its importance as a frequent cause of non-syndromic CP across different populations.

PDGFRa mutations in humans with isolated cleft palate

“…However, they still contribute to a small PDGFRa mutations in isolated cleft palate S Rattanasopha et al fraction, approximately 7% of patients. 13,14 To better understand the genetic factors contributing to CP, more susceptible genes are needed to be identified. PDGFRa was previously suggested to have a role in diaphragmatic hernia 15 and total anomalous pulmonary venous return (TAPVR).…”

“…This cohort also included patients who were previously screened for TBX22 mutations as previously reported. 13 There were 44 male and 58 female. Ninetysix cases were sporadic and six cases had a positive family history.…”

The function and regulation of TBX22 in avian frontonasal morphogenesis

“…The high degree of evolutionary conservation was recently confirmed in zebrafish, where expression is also restricted to the perioral mesenchyme (Jezewski et al, 2009). Interestingly, despite the expression of TBX22 in the frontonasal mass, mutations in the human gene primarily affect fusion of the maxillary-derived secondary palate (CPX, OMIM 303400; Braybrook et al, 2001;Marcano et al, 2004;Stanier and Moore, 2004;Suphapeetiporn et al, 2007). Recently, a null mutation of Tbx22 was reported in the mouse and the main phenotypes included submucous cleft palates and posteriorized tongues (Pauws et al, 2009).…”

Regulation of Tbx22 during facial and palatal development

“…Mutations in TBX22 were identified as the cause of a semidominant X-linked craniofacial syndrome, X-linked cleft palate, and ankyloglossia (CPX; OMIM 303400). Mutations include frame shift, splice site, non-sense, and mis-sense mutations, which are thought to result in loss of protein function (Braybrook et al, 2001(Braybrook et al, , 2002Marcano et al, 2004;Chaabouni et al, 2005;Suphapeetiporn et al, 2007). The phenotypic penetrance in patients with TBX22 mutations is highly variable ranging from ankyloglossia alone, to submucous cleft palate, bifid uvula, or cleft of the soft and hard palate with or without ankyloglossia (Marcano et al, 2004).…”

“…The phenotypic penetrance in patients with TBX22 mutations is highly variable ranging from ankyloglossia alone, to submucous cleft palate, bifid uvula, or cleft of the soft and hard palate with or without ankyloglossia (Marcano et al, 2004). Mutations in TBX22 have also been found in sporadic cleft palate patients and are the most common single cause of cleft palate known, causing 4-8% of all cases (Braybrook et al, 2001(Braybrook et al, , 2002Marcano et al, 2004;Chaabouni et al, 2005;Andreou et al, 2007;Suphapeetiporn et al, 2007). In addition sequence variation in the TBX22 promoter has recently been identified as a risk factor for cleft palate (Pauws et al, 2009b).…”