Senior Department of Pediatrics, the Seventh Medical Center of PLA General Hospital, Beijing, China.
Department of Pediatrics, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
Brain Behav. 2023 Dec;13(12):e3290. doi: 10.1002/brb3.3290. Epub 2023 Oct 31.
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.
Sotos 综合征（SS）是一种过度生长疾病，其特征为独特的面部特征、骨龄提前、大头畸形和发育迟缓，与 NSD1 基因的改变有关。本文报道了一例由 NSD1 基因无义突变引起的 SS 患儿。
对先证者及其父母进行全外显子组测序（WES）。Sanger 测序用于确认突变。我们使用 PubMed 进行文献复习，共发现 12 篇文章和 14 例 SS 患者。
患儿表现出 SS 的典型面部特征、手部畸形和癫痫。WES 发现一个新生杂合变异： NSD1（NM_022455.5），c.6095G＞A，p.TRP2032*。我们还复习了 14 例 SS 患者的表型谱，这些患者表现出多种临床表型，包括发育迟缓、癫痫、脊柱侧凸、听力损失、心脏和泌尿系统异常等。
通过文献复习总结了突变部位或类型与表型之间缺乏相关性。NSD1 蛋白含有 14 个功能域，该无义突变位于 SET 结构域。终止密码子的早期出现导致蛋白截断。NSD1 基因的单倍不足导致过度生长障碍。
