De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

摘要: Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms malformation occur sporadically and associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report study Baraitser-Winter syndrome, well-defined disorder characterized by distinct craniofacial features, ocular colobomata neuronal migration defect. Using whole-exome sequencing three proband-parent trios, identified missense changes in the cytoplasmic actin-encoding genes ACTB ACTG1 one two probands, respectively. Sequencing both 15 additional affected individuals disease-causing mutations all including recurrent alterations (ACTB, encoding p.Arg196His, ACTG1, p.Ser155Phe). Our results confirm that trio-based exome is powerful approach discover causing sporadic disorders, emphasize overlapping roles actin proteins development suggest syndrome predominant phenotype mutation these genes.