Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes
Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes
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DOI：
10.1038/ejhg.2013.189
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发表时间：
2014-04-01
影响因子：
5.2
通讯作者：
Genevieve, David
中科院分区：
文献类型：
--
作者：
Doco-Fenzy, Martine;Leroy, Camille;Genevieve, David
肥胖症是一种常见的，但高度，临床和遗传异质性疾病。2号染色体短臂末端区域的缺失是罕见的，文献中约有13例患者报告，通常与Prader-Willi样表型相关。我们报告5个无关的患者与2 p25缺失的父亲起源提出早发性肥胖，食欲过盛，智力不足，行为困难。在这些患者中，3例为原发性纯2 pter缺失，1例为父本derivative der（2）t（2; 15）（p25.3;q26），2 pter区域缺失，最后1例为间质性2 p25缺失。通过SNP阵列或阵列-CGH表征缺失的大小，并通过荧光原位杂交（FISH）研究证实。4例患者共有2p25.3缺失，最小关键区域估计为1.97Mb，包括7个基因，即SH 3 HYL 1，ACP 1，TMEMI 8，SNTG 2，TPO，PXDN和MYT 1 L基因。第五名患者具有较小的间质缺失，包括TPO、PXDN和MYT 1 L基因。使用微卫星标记进行基因分型，确定缺失的父系来源。对缺失区域中包含的基因的分析使我们推测ACP 1、TMEM 18和/或MYT 1 L基因可能参与早发性肥胖。此外，智力缺陷和行为问题可以通过SNTG 2和MYT 1 L基因的杂合丢失来解释。最后，我们讨论了删除的起源。
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 1.97Mb 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.