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.
Assessment of 2q23.1 Microdeletion Syndrome Implicates MBD5 as a Single Causal Locus of Intellectual Disability, Epilepsy, and Autism Spectrum Disorder
Talkowski, M. E. et al. (2011). The American Journal of Human Genetics, 89,551-563.
This article is important due to its large observation group of sixty-five symptomatic individuals. By assessing each chromosome deletion, it is believed MBD5 is the single causal locus for individuals with these groups of symptoms. The paper specifically displays charts comparing individuals with MBD5 specific disruption and that of 2q23.1 deletions. In doing so, it presents a list of numerous characteristic that individuals with this condition may have. It is important to view this list as a sense of potential health risks and to help predict needed therapies and services your child may need in the future. Interestingly, it also discusses the condition overlap with autism spectrum disorders and the need for accurate chromosomal diagnosis.
Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures
Williams, S. R. et. al. (2010). European Journal of Human Genetics, 18: 436-441; doi: 10.1038/ejhg.2009.199.
This article displays information needed to categorize the common physical characteristics as well as behavioral and intellectual disabilities associated with the disorder. Discussing in detail two individual cases, they are compared to several previously observed individuals with similar deletions. The article shows pictures of the two female subjects to visually display the clinical features associated with the condition.
SV Mullegama and SH Elsea (2016) European Journal of Human Genetics (2016) 24, 1235–1243; doi:10.1038/ejhg.2016.35; published online 25 May 2016
MBD5-associated neurodevelopmental disorder (MAND) is an umbrella term that describes a group of disorders, 2q23.1 deletion syndrome, 2q23.1 duplication syndrome, and MBD5 variants, that affect the function of methyl-binding domain 5 (MBD5) and share a common set of neurodevelopmental, cognitive, and behavioral impairments. This review provides a comprehensive clinical and molecular synopsis of 2q23.1 deletion syndrome. Approaches to diagnosis, genetic counseling, and up-to-date management are summarized, followed by a discussion of the molecular and functional role of MBD5. Also included is a brief summary of MBD5 variants that affect function of MBD5 and 2q23.1 duplication syndrome.