retardation found mutations in BAF250B (ARID1B), which were also heterozygous in most cases. Because the issue of tumor heterogeneity can often inaccurately skew the determination of whether one or both alleles are inactivated, the discovery of the heterozygous BAF250B mutations in patients with these neurologic conditions was conceptually informative, lending further grounds to consider heterozygous mutations as causative candidates and prompting studies to identify the mechanism of allelic dominance. Thus, it appears that a fundamental mechanism for the prevention of cancer and the development of the human nervous system relies on two functional copies of the BAF250A and B family, respectively. Because BAF250 is not necessary for in vitro chromatin remodeling, it appears that this critical, dosage-sensitive function is independent of the limited set of chromatin regulatory events that can be monitored by in vitro chromatin remodeling experiments on nucleosomal templates, strongly suggesting the need for new assays for the function of ATP-dependent chromatin regulatory complexes.
