Sureni V Mullegama et al. The European Journal of Human Genetics (2013), 1–7
This article describes a new chromosome duplication syndrome, 2q23.1 duplication. This duplication includes the MBD5 gene, the same gene involved in the 2q23.1 deletion syndrome. Some chromsomal regions contain genes that are sensitive to level of expression. When these chromosomal regions are deleted or duplicated, they result in copy number differences for the genes affected. The resulting abnormal gene dosage plays an important role in the genetic etiology of the neurodevelopmental disorder associated with the specific chromosomal abnormality. When the dosage sensitive genes are not expressed at the right level, intellectual disability (ID), autism, seizures, and other behavioral and developmental problems can development. In this paper, 23 individuals with 2q23.1 duplications are described, establishing a new duplication syndrome. The observed characteristics include ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (outer ear anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. The features of the previously reported 2q23.1 deletion syndrome are primarily due to reduced expression, or haploinsufficiency, of MBD5. Individuals with 2q23.1 duplication syndrome have a slightly less severe phenotype than the reciprocal 2q23.1 deletion, consistent with findings in other chromosomal duplication syndromes. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed supportMBD5 as a dosage-sensitive gene critical for normal development.