Bosma arhinia microphthalmia syndrome (BAMS) is a rare congenital disorder characterized by the absence of a nose, along with eye and reproductive anomalies. BAMS is caused by heterozygous missense variants in SMCHD1, an epigenetic regulator. Despite uncovering its genetic basis, the cellular basis of the disease has remained elusive. The embryonic development of the nose involves direct contributions from both the neural crest and cranial placodes. Here, we differentiated patient-derived induced pluripotent stem cells toward the cranial placode lineage and found that they exhibited significant differentiation defects. Combined transcriptome and DNA methylome analyses further revealed dysregulation in cell adhesion but without overt apoptosis. Together our research suggests that BAMS is caused by impaired differentiation to cranial placode cells and changes in cell adhesion, offering new insights into the cellular pathology of this enigmatic syndrome.
Rao et al. (Wed,) studied this question.