Abstract
Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader–Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.
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Acknowledgements
This work was supported by ACLF telomere network (promoter Bordeaux Hospital), the national array-CGH network funded by the French Ministry of Health, and the AOL 2001 project (Reims Hospital), France. This work was supported by grants AOL 2001-2003 CHU Reims and PHRC 2003-2005 CHU-REIMS, and Promoter CHU-Bordeaux France, ACLF réseau télomère. This work was also spported by the grant PHRC N°2007-AOO642-51 CHU Montpellier.
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Doco-Fenzy, M., Leroy, C., Schneider, A. et al. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes. Eur J Hum Genet 22, 471–479 (2014). https://doi.org/10.1038/ejhg.2013.189
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DOI: https://doi.org/10.1038/ejhg.2013.189
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