MSX1 Interacts with PRDM16 in Clefts and Tooth Agenesis

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Objectives: Oral clefts and tooth agenesis are complex defects that appear to share some genetics mechanisms. MSX1 variation has been associated with both defects and an interaction between MSX1 and TGFB3 was suggested for clefts. Potential etiologic cleft missense mutations were identified in PRDM16, a transcriptional co-repressor known to negatively regulate TGFB signaling. In this study we sought to determine if there is statistical evidence that interactions between MSX1 and PRDM16 contribute to isolated clefts and isolated tooth agenesis. Methods: Blood and/or cheek swab samples were obtained for DNA analysis from 110 and 116 case/parent trios of cleft and tooth agenesis families, respectively. Cleft probands had isolated cleft lip with or without cleft palate and tooth agenesis probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using SSCP or kinetic PCR assays. Transmission distortion tests of the marker alleles were performed. Results: There was statistically significant data (Table) that suggests MSX1 interacts with PRDM16 (Table. Note: T/NT=transmitted/non-transmitted). Conclusion: These findings suggest that MSX1 and PRDM16 play a role in isolated cleft lip and palate and isolated dental agenesis in humans. NIH grants R37- R37-DE08559.