PDF(Pubmed)
Abstract：
Sotos syndrome (SS) is an overgrowth disease characterized by distinctive facial features, advanced bone age, macrocephaly, and developmental delay is associated with alterations in the NSD1 gene. Here, we report a case of a 4-year-old female child with SS caused by NSD1 gene nonsense mutation.
Whole-exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubMed and found 12 articles and 14 patients who presented with SS.
The patient showed typical facial features of SS, hand deformities, and seizure. WES revealed de novo heterozygous variant: NSD1 (NM_022455.5), c.6095G > A, p.TRP2032*. We also reviewed the phenotype spectrum of 14 patients with SS, who exhibited a variety of clinical phenotypes, including developmental delay, seizures, scoliosis, hearing loss, cardiac and urinary system abnormalities, and so on.
The lack of correlation between mutation sites or types and phenotypes was summarized by literature reviewing. The NSD1 protein contains 14 functional domains and this nonsense mutation was located in SET domain. Early appearance of the termination codon leads to protein truncation. Haploinsufficiency of the NSD1 gene causes the overgrowth disorders.
Whole-exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubMed and found 12 articles and 14 patients who presented with SS.
The patient showed typical facial features of SS, hand deformities, and seizure. WES revealed de novo heterozygous variant: NSD1 (NM_022455.5), c.6095G > A, p.TRP2032*. We also reviewed the phenotype spectrum of 14 patients with SS, who exhibited a variety of clinical phenotypes, including developmental delay, seizures, scoliosis, hearing loss, cardiac and urinary system abnormalities, and so on.
The lack of correlation between mutation sites or types and phenotypes was summarized by literature reviewing. The NSD1 protein contains 14 functional domains and this nonsense mutation was located in SET domain. Early appearance of the termination codon leads to protein truncation. Haploinsufficiency of the NSD1 gene causes the overgrowth disorders.
摘要：
背景：Sotos综合征（SS）是一种以独特的面部特征为特征的过度生长疾病，先进的骨龄，大头畸形,发育迟缓与NSD1基因的改变有关。这里,我们报告了一例4岁女性儿童由NSD1基因无义突变引起的SS。
方法：对先证者及其父母应用全外显子组测序（WES）。使用Sanger测序来确认突变。我们使用PubMed进行了文献综述，发现12篇文章和14例出现SS的患者。
结果：患者表现出典型的SS面部特征，手部畸形,和癫痫。WES显示从头杂合变体：NSD1（NM_022455.5），c.6095G>A，P.TRP2032*。我们还回顾了14例SS患者的表型谱，表现出多种临床表型，包括发育迟缓,癫痫发作,脊柱侧弯,听力损失,心脏和泌尿系统异常，等等。
结论：通过文献综述总结了突变位点或类型与表型之间缺乏相关性。NSD1蛋白含有14个功能结构域,并且该无义突变位于SET结构域中。终止密码子的早期出现导致蛋白质截短。NSD1基因的单倍体不足导致过度生长障碍。
方法：对先证者及其父母应用全外显子组测序（WES）。使用Sanger测序来确认突变。我们使用PubMed进行了文献综述，发现12篇文章和14例出现SS的患者。
结果：患者表现出典型的SS面部特征，手部畸形,和癫痫。WES显示从头杂合变体：NSD1（NM_022455.5），c.6095G>A，P.TRP2032*。我们还回顾了14例SS患者的表型谱，表现出多种临床表型，包括发育迟缓,癫痫发作,脊柱侧弯,听力损失,心脏和泌尿系统异常，等等。
结论：通过文献综述总结了突变位点或类型与表型之间缺乏相关性。NSD1蛋白含有14个功能结构域,并且该无义突变位于SET结构域中。终止密码子的早期出现导致蛋白质截短。NSD1基因的单倍体不足导致过度生长障碍。
