Mutations in MSX1, PAX9 and MMP20 genes in Saudi Arabian patients with tooth agenesis

Tooth agenesis in human being is the most common congenital anomaly associated with dental development. Mutations in many genes such as MSH homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin A (EDA) and EDA receptor (EDAR) have been associated with familial form of this condition. However, in large majority of patients, genetic cause could not be identified. The primary aim of present study was to identify the causative mutation(s) in these genes in Saudi Arabian families diagnosed with non-syndromic form of disease. Direct sequencing of coding regions, including exon-intron boundaries of these genes was carried out. All identified nucleotide variations were also tested to exclude possibility of being rare polymorphisms. The sequence analysis of exons and exon-intronic regions of these genes revealed five new mutations that include four in MSX1, one in PAX9 and one single nucleotide polymorphism (SNP) in majority of the patients in MMP20. One novel mutation in exon 1 of MSX1 gene (5354C > G; A40G) was found in three patients. In addition, another novel mutation was detected in two patients in exon 3 (PAX9) as g.10672A > T which changes asparagine to isoleucine at position 40. These mutations were not found in any of the control subjects. A single SNP in MMP20 genes (g.5066A > C) that changes lysine to threonine at position 18 was found in 10% controls as well. Our results for the first time demonstrates that mutations in MSX1 gene might play an important role in hypodontia cases involving pre-molars and is a risk factor for this ethnic population mainly of Arabs and is first report linking these mutations with tooth agenesis.