目的:Sotos综合征(SOTOS)是一种罕见的遗传病,表现出以下独特特征:产前过度生长,面部异常,智力残疾。这种疾病通常与核受体结合SET结构域蛋白1(NSD1)基因的单倍体不足有关。我们调查了4例以早发性过度生长和发育迟缓为特征的儿科病例。这项研究的主要目的是实现准确的遗传诊断。
■一种包括染色体核型分析的序贯分析方法,整个外显子组测序,并进行微阵列分析。
结果:所有4例病例均表现出NSD1基因变异,通过鉴定四个以前未报告的从头变体,每个具体到一个案例。具体来说,案例1携带NSD1(NM_022455):c.2686C>T(p。Q896X)变体,案例2具有NSD1(NM_022455):c.2858_2859delCT(p。3953X)变体,病例3显示染色体畸变,chr5:5q35.2q35.3(176,516,604-176,639,249)×1,包含NSD1的5'-非翻译区,案例4包含NSD1(NM_022455):c.6397T>G(p。C2133G)变体。
结论:这项研究不仅为这些病例提供了精确的诊断,而且为促进知情咨询提供了重要的证据。此外,我们的发现扩大了与SOTOS相关的突变范围.
OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses.
UNASSIGNED: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted.
RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5\'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant.
CONCLUSIONS: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.