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Review
. 2014 Jul 24:1:14001.
doi: 10.1038/hgv.2014.1. eCollection 2014.

Clinical impacts of genomic copy number gains at Xq28

Toshiyuki Yamamoto  1 , Keiko Shimojima  2 , Shino Shimada  1 , Kenji Yokochi  3 , Shinsaku Yoshitomi  4 , Keiko Yanagihara  5 , Katsumi Imai  4 , Nobuhiko Okamoto  6
Affiliations
Review

Clinical impacts of genomic copy number gains at Xq28

Toshiyuki Yamamoto et al. Hum Genome Var. .

Abstract

Duplications of the Xq28 region are the most frequent chromosomal aberrations observed in patients with intellectual disability (ID), especially in males. These duplications occur by variable mechanisms, including interstitial duplications mediated by segmental duplications in this region and terminal duplications (functional disomy) derived from translocation with other chromosomes. The most commonly duplicated region includes methyl CpG-binding protein 2 gene (MECP2), which has a minimal duplicated size of 0.2 Mb. Patients with MECP2 duplications show severe ID, intractable seizures and recurrent infections. Duplications in the telomeric neighboring regions, which include GDP dissociation inhibitor 1 gene (GDI1) and ras-associated protein RAB39B gene (RAB39B), are independently associated with ID, and many segmental duplications located in this region could mediate these frequently observed interstitial duplications. In addition, large duplications, including MECP2 and GDI1, induce hypoplasia of the corpus callosum. Abnormalities observed in the white matter, revealed by brain magnetic resonance imaging, are a common finding in patients with MECP2 duplications. As primary sequence analysis cannot be used to determine the region responsible for chromosomal duplication syndrome, finding this region relies on the collection of genotype-phenotype data from patients.

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Figures

Figure 1
Figure 1
The genome map around Xq28. (a) A scheme of X chromosome downloaded from the UCSC genome browser. (b) Duplication regions identified in 11 patients are integrated by custom track and shown by grey bars. (c) Xq28 region is expanded. Examples of relevant genes are shown by black rectangles. Critical regions for distinct clinical features and segmental duplication regions are shown by red arrows and blue hexagons.
Figure 2
Figure 2
Brain magnetic resonance imaging (MRI) findings of new patients with Xq28 duplications. Sagittal T1 (up) and axial T2 (bottom)-weighted images are shown. All patients showed hypoplasia of the corpus callosum and T2 signal high intensities in the deep white matter. Three patients (other than patient 8) showed atrophies of the cerebellum and bilateral dilatations of the lateral ventricles, indicating age-dependent progression. Patient 3 showed a translucent septal defect, and patients 5 and 8 showed a verga cavity.
See this image and copyright information in PMC

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