Japanese Mental Retardation Consortium. 2012. Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation

Department of Molecular Cytogenetics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Journal of Human Genetics (Impact Factor: 2.46). 12/2011; 57(1):73-7. DOI: 10.1038/jhg.2011.131
Source: PubMed


Investigations of chromosomal rearrangements in patients with mental retardation (MR) are particularly informative in the search for genes involved in MR. Here we report a family with concomitant duplications of methyl CpG binding protein 2 (MECP2) at Xq28 and ATRX (the causative gene for X-linked alpha thalassemia/mental retardation) at Xq21.1 detected by array-comparative genomic hybridization. The alterations were observed in a 25-year-old man who inherited them from his mother, who showed a normal phenotype and completely skewed X-chromosome inactivation, and also in his cousin, a 32-year-old man. The proband and his cousin showed severe MR, muscular hypotonia, recurrent respiratory infections and various other features characteristic of MECP2 duplication syndrome. However, the proband also had cerebellar atrophy never reported before in MECP2 duplication syndrome, suggesting that his phenotypes were modified through the ATRX duplication in an additive or epistatic manner.

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Available from: Eiji Nakagawa, Apr 23, 2014
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    • "Such mutations are commonly distinguished from low-level gains/losses using a direct threshold of array data. However, the threshold value often differs greatly, ranging from a log2 ratio of +/−0.4 for some studies [46,47] to as high as +/−1.0 for others [48,49]. The criteria we used to detect deletions were based on the aCGH patterns obtained from our mutant versus wild type hybridizations. "
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    • "Mutations as well as deletions of either one of those genes alone result in severe intellectual disability and autism, while no clinical impact of increased dosage of a unique gene other than MECP2 in the duplicated interval has been reported (Lugtenberg et al., 2009). It is possible the phenotypes in the probands are modified through an additive or epistatic effect between MECP2 and other genes within Xq28 duplication (Honda et al., 2012). Overall, the phenotype in our case manifested the hallmark of MECP2 duplication syndrome. "
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