Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures

Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
European journal of human genetics: EJHG (Impact Factor: 4.23). 11/2009; 18(4):436-41. DOI: 10.1038/ejhg.2009.199
Source: PubMed

ABSTRACT Microdeletion of chromosome 2q23.1 results in a novel syndrome previously reported in five individuals. Many of the del(2)(q23.1) cases were thought to have other syndromes such as Angelman, Prader-Willi, or Smith-Magenis because of certain overlapping clinical features. We report two new cases of the 2q23.1 microdeletion syndrome, describe the syndrome phenotype, define the minimal critical region, and analyze the expression of critical region genes toward identification of the causative gene(s) for the disorder. Individuals with del(2)(q23.1) have severe developmental and cognitive delays, minimal speech, seizures, microcephaly, mild craniofacial dysmorphism, behavioral disorders, and short stature. The deletions encompassing 2q23.1 range from >4 Mb to <200 kb, as identified by oligonucleotide and BAC whole-genome array comparative hybridization. The minimal critical region includes a single gene, MBD5, deleted in all cases, whereas all but one case also include deletion of EPC2. Quantitative real-time PCR of patient lymphoblasts/lymphocytes showed an approximately 50% reduced expression of MBD5 and EPC2 compared with controls. With similar phenotypes among the 2q23.1 deletion patients, the idea of one or more common genes causing the pathological defect seen in these patients becomes evident. As all five previous cases and the two cases in this report share one common gene, MBD5, we strongly suspect that haploinsufficiency of MBD5 causes most of the features observed in this syndrome.

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Available from: Sarah H Elsea, Aug 21, 2015
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    • "MBD proteins modulate gene expression by recruiting various partners involving in chromatin remodelling (Bogdanovic & Veenstra, 2009). Although the precise function of MBD5 is poorly understood , it was recently implicated in a human disease syndrome that includes autism spectrum disorder, microcephaly, intellectual disability, severe speech impairment, and seizures (Williams et al, 2010; Chung et al, 2011; Talkowski et al, 2011; Cukier et al, 2012; Ladha, 2012; Noh & Graham, 2012; Bonnet et al, 2013; Shichiji et al, 2013; Hodge et al, 2014; Mullegama et al, 2014). Deletion of Mbd5 in mice causes similar developmental retardation and disturbed glucose homeostasis (Du et al, 2012). "
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