Autism spectrum disorders (ASDs) are typically characterized by persistent social deficits and can include a wide array of symptoms including intellectual disability, repetitive or stereotyped behaviors, difficulties with social communication, as well as countless others symptoms. While some ASDs have been shown to be heritable disorders, such as Fragile X Syndrome, others have yet to be identified as such. Instead, many ASDs are thought to be caused by de novo mutations. Further adding to the complexity of these disorders is the fact that the de novo can be highly variable even within a specific disorder, making it difficult to find treatments and cures. One disorder caused by de novo mutations is the 2q23.1 microdeletion syndrome. As the …show more content…
In 2011, Michael Talkowski and colleagues found 65 patients with mutations in the MBD5 gene, which lies in the 2q23.1 region. Of those 65 patients, 63 cases involved a heterozygous deletion of the gene while the other two involved translocations. All patients presented with intellectual disability, motor delay, seizures, language impairment, and autistic-like features. Additionally, there were common dysmorphic features including thin upper lip, poor vision, and abnormalities consistent with 2q23.1 microdeletion syndrome. Most notably, it has been shown extremely small microdeletions that consist of only the MBD5 region, or a single base pair mutation of the MBD5 which cause the same set of symptoms as the larger mutations which encompass multiple gene regions such as ORC4 and EPC2 (PMC3188839). This was further confirmed by Bregje van Bon which showed that of the 15 varying genes affected by the microdeletion, MBD5 was the only overlap in all patients. Ultimately, this helped to implicate MBD5 as the causative gene in MBD5 syndrome. Prior to this knowledge, diagnosis relied solely on clinical impressions, however diagnosis now includes a genetic test for MBD5 abnormalities for proper …show more content…
MBD was initially identified as a small part of the MeCP2 protein that was required to bind methylated DNA (PMC2729420). Most genes in the MBD family play important roles in transcriptional repression, as well as heterochromatin formation (PMC2729420). MBD1 and MBD2 silence transcription via repression domains, while MBD3 and MBD4 are involved in chromatin remodeling and DNA repair, respectively (PMC2729420). However, MBD5 has been found to bind to non-heterochromatin regions, unlike the other members of the MBD family (PMC4154127). Additionally, it has been suggested that although MBD5 cannot bind directly to methylated DNA, it is possible for MBD5 to contribute to the formation of heterochromatin (PMC3188839). It is thought that MBD5 may be able to bind to a DNA complex since it has been shown to interact directly with myocyte enhancer-binding factor 2C (MEF2C), which plays roles in both regulation of neuronal genes as well as development and neurogenesis (PMC3188839). Interestingly, haploinsufficiency of MEF2C, which is associated with a 5q14.3 microdeletion, results in an ASD phenotype that shares strikingly similar characteristics with 2q23.1 microdeletion. Overlapping symptoms include hypotonia, seizures, intellectual disability, and autistic-like features (PMC3188839). These findings suggest that MEF2C and MBD5 may share a common neurogenesis