The genotypic and phenotypic features of familial tooth agenesis in consanguineous families.

PhDAn evolution in methods of identifying the causal mutations and candidate genes for Mendelian disorders has occurred recently. Though several studies have reported the causative mutations in non syndromic tooth agenesis, there are only two reports on autosomal recessive nonsyndromic tooth agenesis in consanguineous families. Since the consanguinity rate is high in tribal population of Saudi and Pakistan, this study identified consanguineous families in these populations to investigate the molecular basis of tooth agenesis. This study aimed to study the phenotype of familial tooth agenesis in Saudi and Pakistani families of consanguineous marriage, and to identify the causative mutations. A further aim was to investigate the influence of the agenesis gene on tooth size in one large Saudi family. Sixteen families with non-syndromic tooth agenesis, were clinically characterised for the pattern of inheritance, tooth agenesis severity and type of teeth affected. Genetic analysis including homozygosity mapping and exome sequencing was performed in eight families. Hand measurements of Saudi family tooth dimensions were made on dental study models. The most affected tooth type in studied families were the lower second premolar and upper lateral incisors. The homozygosity mapping approach failed to identify the regions of the diseased mutations in these families. The exome sequencing data revealed a heterozygous novel frameshift mutation in exon 2 of the MSX1 gene, c.750_751insACCGGCTGCC (p.A250fs) in one Saudi family and a homozygous novel mutation in exon 8 of the SMOC2 gene, c.681T>A (p.C227X), in the Pakistani family. It was found that there was a significant (p <.0.05) trend of reduction in the crown sizes both in the tooth agenesis group and their family members with no tooth agenesis compared to the control group. It is concluded that homozygosity mapping was not sensitive to identify the elusive tooth agenesis gene and whole exome sequencing technique is needed in future studies. The tooth measurement study indicates and confirms that crown size is closely related to tooth agensis.Saudi Ministry of Higher Education; Saudi Cultural Bureau in the U