Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Republic of Korea.
Department of Surgery, Jeju National University Hospital, Jeju, Republic of Korea.
Pediatr Res. 2017 Jul;82(1):87-92. doi: 10.1038/pr.2017.106. Epub 2017 May 3.
BackgroundSotos syndrome (SoS) is an overgrowth disorder with various congenital anomalies and is usually accompanied by other clinical problems. However, anorectal malformations have not been documented as part of the SoS entity. Our objective is to report on a case of SoS associated with Hirschsprung's disease (HSCR) and subsequent genetic analysis.MethodsA 2-year-old boy with SoS experienced constipation since infancy and ultimately showed an aganglionic segment in the histopathologic examination, which was followed by exome-sequencing analysis.ResultsIn the genetic test for SoS diagnosis, two novel mutations of NDS1, c.2465C>A (p.Ser822Tyr) and c.4347T>A (p.Cys1449*), were observed and verified by resequencing in the patient and his parents. In further whole-exome-sequencing analysis using the patient's blood DNA, which was followed by a comparison analysis with the results of our previously reported genome-wide association study (GWAS) of HSCR, three genes (ZNF827, FGD2, and KCNJ12) with significance for HSCR from our previous GWAS were overlapped among the genes showing variants in the exome sequencing.ConclusionThis is the first reported patient with SoS and HSCR. Further studies are required to determine whether there is a genetic relationship between SoS and HSCR.
Sotos 综合征（SoS）是一种伴有多种先天畸形的过度生长障碍，通常伴有其他临床问题。然而，肛门直肠畸形并未被记录为 SoS 实体的一部分。我们的目的是报告一例与先天性巨结肠（HSCR）相关的 SoS 病例，并进行后续的遗传分析。
一名 2 岁的 SoS 患儿自婴儿期起即出现便秘，最终在组织病理学检查中显示出无神经节细胞段，随后进行了外显子组测序分析。
在 SoS 诊断的基因检测中，观察到 NDS1 的两个新突变，c.2465C>A（p.Ser822Tyr）和 c.4347T>A（p.Cys1449*），并通过对患者及其父母的重新测序进行了验证。在使用患者血液 DNA 进行的进一步全外显子组测序分析中，与我们之前报道的 HSCR 全基因组关联研究（GWAS）结果进行了比较分析，在基因中发现了变异，其中三个基因（ZNF827、FGD2 和 KCNJ12）与我们之前的 GWAS 中 HSCR 的显著性相关。
这是首例报道的 SoS 和 HSCR 患者。需要进一步研究以确定 SoS 和 HSCR 之间是否存在遗传关系。
