Jeske M Bij de Weg, Marjon A de Boer, Cynthia Meijer, Noëlle Lugtenburg, Marijke Melles, Johanna I P de Vries, Christianne J M de Groot
The value of a mobile educative Application additional to Standard counselling on aspirin Adherence in Pregnancy: the ASAP study, a randomised controlled trial
PEC innovation
one common structural birth defects orofacial clefts ofcs studied decades recent studies demonstrated genetic differences different phenotypic presentations ofcs however contribution rare genetic variation genomewide different subtypes ofcs understudied studies focusing common genetic variation rare variation within targeted regions genome therefore used wholegenome sequencing data gabriella miller kids first pediatric research program conduct genebased burden analysis test genetic modifiers cleft lip cl vs cleft lip palate clp found significantly increased burden rare variants sec24d cl cases compared clp cases p686107 15 variants within sec24d 533 synonymous overlapped known craniofacial enhancer tested whether variants could alter predicted transcription factor binding sites tfbs found rare alleles destroyed binding sites 9 transcription factors tfs including pax1 p00009 created binding sites 23 tfs including pax6 p612105 pax9 p 00001 known involved normal craniofacial development suggesting potential mechanism synonymous variants could functional impact overall study demonstrates rare genetic variation contributes phenotypic heterogeneity ofcs suggests regulatory variation may also contribute warrant investigation future studies genetic variants controlling risk ofc