De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay
De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay
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DOI：
10.1016/j.gene.2013.10.001
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发表时间：
2014-01-01
期刊：
影响因子：
3.5
通讯作者：
Li, Ling-Hui
中科院分区：
文献类型：
--
作者：
Lin, Dar-Shong;Chuang, Tzu-Po;Li, Ling-Hui
男性中包含甲基CpG结合蛋白2（MECP 2）的Xq 28重复序列表现出独特的表型，包括发育迟缓、面部畸形、肌肉张力减退、智力残疾、言语障碍或缺失、复发性感染和早期死亡。绝大多数受影响的男性从他们通常无症状的携带者母亲那里继承了MECP 2重复。只有少数情况下，Xq 28重复起源于de nova不平衡的X/Y易位已被报道，并在相关文献中，只有三名男性的父亲起源的畸变已被验证。在这里，我们提出了一个核型正常的男性特征的MECP 2重复综合征。全基因组SNP基因分型显示从Xq 28到末端的从头2.26-Mb重复。重复区域内的SNP的基因型指示父系起源。荧光原位杂交（fluorescence in situ hybridization，FISH）结果显示，在精子发生过程中存在一种新的Xq：Yp易位，其特征为der（Y）t（Y;X）（p11.32;q28）。表型与先前报道的Xq 28重复起源于不平衡的X/Y易位的病例进行比较，并且没有特定的表型部分可以促成亲本不平衡的起源。本报告进一步强调了高分子细胞遗传学方法，如SNP阵列和FISH，在鉴定亚显微重排，结构配置和异常的父母起源，而在评估儿童特发性发育迟缓和智力残疾的能力。(C)2013爱思唯尔有限公司版权所有。
Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de nova unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability. (C) 2013 Elsevier B.V. All rights reserved.