Background Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD 1 gene has been implicated as the major cause of Sotos ...Background Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD 1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome. Methods Thirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing. Results NSD1 gene mutations were detected in 26 （72%） Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations （6 frameshift, 8 nonsense, 2 spice site, and 7 missense）. Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome. Conclusions Most cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.展开更多
The nuclear receptor-binding SET domain-containing protein 1 (NSD1) is a Histone-lysine N-methyltransferase (HMTase), which catalyzes mono-and di-methylation of H3K36.
组蛋白的修饰通过调节染色质结构的疏密程度从而影响基因转录等与DNA有关的生物学功能。NSD蛋白家族(nuclear receptor binding SET domain proteins)(包括NSD1-3)是一组与肿瘤发生相关的组蛋白甲基化转移酶,其中又以NSD2与肿瘤的关系...组蛋白的修饰通过调节染色质结构的疏密程度从而影响基因转录等与DNA有关的生物学功能。NSD蛋白家族(nuclear receptor binding SET domain proteins)(包括NSD1-3)是一组与肿瘤发生相关的组蛋白甲基化转移酶,其中又以NSD2与肿瘤的关系最为密切。近年来的研究发现,NSD2在多发性骨髓瘤、神经母细胞瘤及肝癌等多种肿瘤中高表达,并且相关病人的预后较差。NSD2呈现多种原癌基因的特征:NSD2高表达促进细胞增殖、克隆形成、侵袭能力增强以及肿瘤移植物的生长等。然而,NSD1与NSD3虽然可以与核孔蛋白98 k Da(nucleoporin 98 k Da,NUP98)形成融合蛋白,在部分急性髓性白血病中有致瘤作用,但是它们本身却具有抑癌基因的特点。该文就NSD蛋白家族的最新研究进展作一综述,阐述了NSD蛋白家族在肿瘤发生发展中的作用及潜在的应用前景。展开更多
文摘Background Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD 1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome. Methods Thirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing. Results NSD1 gene mutations were detected in 26 （72%） Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations （6 frameshift, 8 nonsense, 2 spice site, and 7 missense）. Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome. Conclusions Most cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.
文摘The nuclear receptor-binding SET domain-containing protein 1 (NSD1) is a Histone-lysine N-methyltransferase (HMTase), which catalyzes mono-and di-methylation of H3K36.
文摘组蛋白的修饰通过调节染色质结构的疏密程度从而影响基因转录等与DNA有关的生物学功能。NSD蛋白家族(nuclear receptor binding SET domain proteins)(包括NSD1-3)是一组与肿瘤发生相关的组蛋白甲基化转移酶,其中又以NSD2与肿瘤的关系最为密切。近年来的研究发现,NSD2在多发性骨髓瘤、神经母细胞瘤及肝癌等多种肿瘤中高表达,并且相关病人的预后较差。NSD2呈现多种原癌基因的特征:NSD2高表达促进细胞增殖、克隆形成、侵袭能力增强以及肿瘤移植物的生长等。然而,NSD1与NSD3虽然可以与核孔蛋白98 k Da(nucleoporin 98 k Da,NUP98)形成融合蛋白,在部分急性髓性白血病中有致瘤作用,但是它们本身却具有抑癌基因的特点。该文就NSD蛋白家族的最新研究进展作一综述,阐述了NSD蛋白家族在肿瘤发生发展中的作用及潜在的应用前景。
