New molecular aspects in the mechanism of oromaxillofacial cleft prevention by B-vitamins.

Clinical and experimental studies show a clear positive effect of B-vitamins in the prevention of oromaxillofacial clefts, especially cleft lip and palate (CL/P). Hereby the local effect of thiamin (B1) in the amniotic fluid is very important for the embryonic facial development as seen in palatal organ models stimulated by topical B-vitamin application (Scheller et al., 2013a). Moreover a low B1 concentration in the serum and amniotic fluid was found in pregnant mice with clefts in their offspring (Scheller et al., 2013b). Immunochemical analyses of midface sections (ThTr-1 transporter) and the placenta (ThTr-2 transporter) of cleft fetuses with orofacial clefts showed an atypical cytoplasmatic localization (Scheller et al., 2017). mRNA nalyses of different B-vitamin transporters (B1, B2, B5, B7, B9) were performed and showed ThTr2 transporter in a short splice variant in all cleft fetuses. This splice variant may cause a functional loss of the transport capacity through the placenta barrier and result in a low amniotic fluid concentration of vitamin B1. All other analyzed transport proteins showed no functional change. These findings confirm the hypothesis that cleft prevention by high vitamin B1 substitution fails in genetically determined cleft mice, caused by an insufficient B1 uptake and missing local effect.