Transforming growth factor-alfa gene (TGFA), human tooth agenesis, and evidence of segmental uniparental isodisomy.

We have previously reported an association between variants in the transforming growth factor-alfa gene (TGFA) and human tooth agenesis. To demonstrate in greater detail that TGFA contributes to tooth agenesis, we investigated additional markers in the gene. Cheek swab samples were obtained for DNA analysis from 116 patient/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using TaqMan assays. Linkage disequilibrium analysis and test of the transmission distortion of the marker alleles were performed. We confirmed that TGFA variants and haplotypes are associated with tooth agenesis. Moreover, it appears that preferential premolar agenesis is associated with TGFA, and patients with a family history of tooth agenesis would have an associated haplotype. Finally, we excluded that a TGFA microdeletion could cause sporadic agenesis in a case of upper lateral incisors and lower second premolars and suggest this case may be consequence of a segmental uniparental isodisomy.