Tooth agenesis is among the well-recognized morphological anomalies in humans. Peg-shaped teeth are a hereditary dental disorder called microdontia, a condition where one or more teeth appear smaller than average (microdontia) [1]. In general, the most common teeth affected are the upper lateral incisors or sometimes third molars. Moreover, it might be seen on both sides in most instances, and they have shorter roots than usual teeth [2]. Peg-shaped teeth are characterized by autosomal dominant inheritance that might cause defects during teeth development. As a result, there is an insufficient development compared to normal development. The prevalence of agenesis in the permanent dentition, excluding the third molars, ranges between 0.15 and 16.2% [3] with a higher prevalence in females than males [4,5,6]. Hua et al. [7] reported that women were 1.35 times more likely than men to have peg-shaped maxillary permanent upper lateral incisors. In general, the prevalence of peg-shaped teeth is about 1.8% [7]. The prevalence of tooth agenesis in permanent teeth in both genders varies among different populations. For example, in Europe the prevalence is 4.6% in males and 6.3% in females; in North American Caucasians is 3.2% in males and 4.6% in females. Meanwhile, the prevalence was the highest in Australia (males 5.5% and females 7.6%) [8].
Odentogenesis undergoes restricted genetic and morphological manipulation depending on cell–cell interactions resulting in the initiation and generation of tooth induced by morphological signaling pathway [9, 10]. Thus, any defect in the germ tooth can lead to dental anomalies either in shape, number, structure, or size of the teeth which exhibit morphological anomalies in humans [11]. Numerous genes and signaling pathways participate in tooth formation and cell differentiation at specific stages of odentogenesis [12] which may cause mutation in tooth agenesis [13]. Dental anomalies could be a combination between genetic, epigenetic and environmental factors during the process of dental development [14]. There are many genes involved in peg-shaped teeth. More than 350 genes have been associated with teeth development such as PAX9, MSX1, AXIN2, EDA, EDAR and WNT10a [15]. However, few genetic studies reported how genes are related to this disorder. In Jordanian population, the effect of MSX1 variation on the peg-shaped teeth is still not clear. The rate of persons with peg-shaped teeth disorder has been increased with a lack of information about the causes of this disorder and occurrence. According to several studies on this disorder, various environmental factors have been investigated in details with very restricted attention has been paved to the genetic component factor [1]. Therefore, a multi genetic factorial epidemiology study has been actually focusing on the genetic aspects including several genes such as MSX1 [16].
Expression assays and transgenic mouse phenotypes revealed that MSX1 has a critical role in craniofacial development [17]. The MSX1 is expressed in the mesenchyme of developing tooth germ especially at the bud and cap stages as a response to epithelial signals [18]. Muscle segment homebox is a non-clustered home box protein, which is located in the small arm of chromosome 4 (chromosome 4p16.2) [19]. It contains two exons which are separated by an intron. The MSX1 is a member of the mammalian MSX gene family, which consists of three physically unlinked members (MSX1, MSX2, and MSX3). MSX genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice [20]. The MSX1 is a protein that in humans is encoded by MSX1 [21]. The encoded protein acts as transcription factors repressor during morphogenesis through interaction with components of the core transcription component complex and other home proteins. Phenomena caused by the lack of MSX1 protein may depend on the localization of the mutations and their effect on the protein structure and function. Moreover, a polymorphism in the MSX1 leads to hypodontia and most of the affected teeth were second premolar and third molar. In addition, the upper lateral incisor, upper first molar, lower central incisor, and lower first molar could be absent [17, 22]. For example, mice with a homozygous deletion of MSX1exhibit a complete cleft palate and failure of tooth development [23].
The objective of this study was to investigate the genetic association of the MSX1 and its susceptibility to the peg-shaped teeth in 36 families and case–control samples Jordanian Arab population.
