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Abstract：
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.
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.
摘要：
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.
■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.
