The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region
The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region
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DOI：
10.1038/ng1197-357
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发表时间：
1997-11-01
期刊：
影响因子：
30.8
通讯作者：
Muscatelli, F
中科院分区：
文献类型：
--
作者：
Jay, P;Rougeulle, C;Muscatelli, F
Prader-Willi综合征（PWS）是一种神经遗传性疾病，由15 q11 - 1 - 3区域缺乏正常的父亲贡献引起（1-3）PWS的临床表现是新生儿期短暂的严重肌张力减退，在发育后期观察到智力迟钝、性腺功能减退和肥胖（4）。已经分离出五种从父系等位基因中具有排他性表达的转录物，但这些转录物中没有一种显示出参与PWS 5，6。在这项研究中，我们报告的NDN，一个新的人类印记基因的分离和鉴定，NDN是专门从父亲的等位基因在分析的组织中表达，并位于PWS区域。它编码一种与小鼠脑特异性NECDIN蛋白（7）NDN同源的推定蛋白;与小鼠一样，脑中的表达仅限于有丝分裂后神经元。NDN显示了印迹基因座的几个特征，包括等位基因DNA甲基化和异步DNA复制。在PWS脑和成纤维细胞中完全缺乏NDN表达表明该基因仅从这些组织中的父系等位基因表达，并表明该新基因在PWS中可能起作用。
Prader-Willi syndrome (PWS) is a neurogenetic disorder that results from the absence of a normal paternal contribution to the 15q11-13 region(1-3) The clinical manifestations of PWS are a transient severe hypotonia in the newborn period, with mental retardation, hypogonadism and obesity observed later in development(4). Five transcripts with exclusive expression from the paternal allele have been isolated, but none of these has been shown to be involved in PWS5,6. In this study, we report the isolation and characterization of NDN, a new human imprinted gene, NDN is exclusively expressed from the paternal allele in the tissues analysed and is located in the PWS region. It encodes a putative protein homologous to the mouse brain-specific NECDIN protein(7), NDN; as in mouse, expression in brain is restricted to post-mitotic neurons. NDN displays several characteristics of an imprinted locus, including allelic DNA methylation and asynchronous DNA replication, A complete lack of NDN expression in PWS brain and fibroblasts indicates that the gene is expressed exclusively from the paternal allele in these tissues and suggests a possible role of this new gene in PWS.