Sotos综合征2例报道及文献复习

doi:10.3969/j.issn.1673-8640.2018.04.018

摘要/Abstract

摘要：

目的对2例疑似Sotos综合征的患儿进行分子诊断,以寻找病因、明确临床诊断,并分析其基因型与表型的关系。方法 2例患儿均来自于上海儿童医学中心医学遗传科门诊,临床主要表现为生长过快、发育落后、头颅巨大,具有特殊面容等遗传病症状。分别对其进行全基因组芯片分析和基因panel测序,并复习相关文献,了解基因型与表型的关系。结果 1例患儿通过全基因组芯片分析,发现在5q35.2-q35.3区存在1个1 907 kb的杂合性缺失,内含NSD1基因,确诊为5q35缺失型Sotos综合征。另1例患儿采用基因panel测序,结果显示NSD1基因存在1个杂合无义突变c.1262G>A, p.Trp421*,诊断为NSD1基因内突变型Sotos综合征,并合并分析了中国内地5例病例的基因型与表型的特征,进一步明确其基因型与表型的关系。结论 Sotos综合征是由NSD1基因变异引起,其临床表现的多样性与NSD1基因异质性高度相关,基因检测有利于提高此类罕见病的临床诊断率。

关键词: Sotos综合征, NSD1基因, 变异, 表型, 基因测序

Abstract:

Objective Molecular diagnosis was performed for 2 suspected cases of Sotos syndrome. To seek the cause of disease and make a definite clinical diagnosis,and to analyze the relationship between genotype and phenotype. Methods Totally,2 children came from the Medical Genetics Department of Shanghai Children's Medical Center,who mainly presented overgrowth,developmental delay,macrocephaly and typical facial appearance. They accepted chromosomal microarray analysis and gene panel test,respectively. Literature review was performed to get to know the relationship between genotype and phenotype. Results A heterozygous microdeletion of 1 907 kb in 5q35.2-q35.3 was found in 1 case by chromosomal microarray analysis,which contained NSD1 gene. This case was confirmed as Sotos syndrome of 5q35 microdeletion. Another case showed a heterozygous nonsense mutation of c.1262G>A,p.Trp421* in NSD1 gene. This case was diagnosed as Sotos syndrome of NSD1 intragenic mutation. Pooled analysis about the features of genotype and phenotype was performed in all 5 inland Chinese cases,which helped us with understanding the relationship between genotype and phenotype. Conclusions NSD1 gene variation causes Sotos syndrome. There is a high relationship between the variety of clinical features and the heterogeneity of NSD1 gene alteration. Gene tests are useful to improve the rate of clinical diagnosis for such rare genetic disease.

Key words: Sotos syndrome, NSD1 gene, Variation, Phenotype, Gene sequencing

中图分类号:

R446.1

陆勇刚, 胥雨菲, 姚如恩, 李牛, 郁婷婷, 王秀敏, 沈亦平, 王剑. Sotos综合征2例报道及文献复习[J]. 检验医学, 2018, 33(4): 353-358.

LU Yonggang, XU Yufei, YAO Ruen, LI Niu, YU Tingting, WANG Xiumin, SHEN Yiping, WANG Jian. Two cases of Sotos syndrome：case report and literature review[J]. Laboratory Medicine, 2018, 33(4): 353-358.

图/表 3

参考文献 22

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病例来源	性别	年龄	特殊面容		生长发育过快			头围	发育落后/智力低下
文献[6]	男	19个月	高额头、眼距宽、外斜视、额颞部毛发稀疏、下颌突出		+			52 cm, >3s	+ 1岁7个月不能主动叫人,对叫名字有反应但迟钝,与人对视交流少
文献[7] 病例1	男	6 h	下颌尖,头颅大		+			38 cm, >2s	+ 5岁时仅会喊爸爸妈妈,不能说完整句子
文献[7] 病例2	男	3 d	不明显		出生时不明显,45个月时身高>同龄儿童平均值的3个s			出生时正常,34 cm	+ 45个月时仅会喊爸爸妈妈, 不能说完整句子
本研究病例1	男	8个月	舟状头,前额突出,前顶头部毛发稀疏,眼距宽,眼裂下斜		+			48.5 cm, >3s	+ 2岁时仅会说短词,与人交流少,不会独走
本研究病例2	男	3岁	头颅大,前额突出,下颌尖长,前顶头部毛发稀疏,眼距宽,眼裂下斜		+			52.8 cm, >2s	+ 17个月会走路,2岁叫妈妈, 目前语言表达少
指标	新生儿黄疸	惊厥	中枢神经系统异常	心血管系统异常		泌尿系统异常	其他	基因型
文献[6]	+	+	脑室扩张	-		-	骨龄超前	5~18外显子缺失,其余未覆盖
文献[7] 病例1	-	-	脑影像实质异常	动脉导管及卵圆孔未闭		阴茎短小、肾盂增宽	手足畸形, 低血糖	NSD1基因完全缺失
文献[7] 病例2	+	-	双侧基底节及额叶受损	卵圆孔未闭		左肾积水	喂养困难, 关节挛缩, 腭裂	5号染色体长臂 NSD1基因区域缺失,具体位点不祥
本研究病例1	+	-	胼胝体发育不良, 脑室偏大	动脉导管未闭		-	手指屈曲畸形	NSD1基因完全缺失
本研究病例2	-	+	脑室扩张,脑水肿可能	动脉导管未闭		-	自闭症倾向	新生无义突变,c.1262G>A

病例来源	性别	年龄	特殊面容		生长发育过快			头围	发育落后/智力低下
文献[6]	男	19个月	高额头、眼距宽、外斜视、额颞部毛发稀疏、下颌突出		+			52 cm, >3s	+ 1岁7个月不能主动叫人,对叫名字有反应但迟钝,与人对视交流少
文献[7] 病例1	男	6 h	下颌尖,头颅大		+			38 cm, >2s	+ 5岁时仅会喊爸爸妈妈,不能说完整句子
文献[7] 病例2	男	3 d	不明显		出生时不明显,45个月时身高>同龄儿童平均值的3个s			出生时正常,34 cm	+ 45个月时仅会喊爸爸妈妈, 不能说完整句子
本研究病例1	男	8个月	舟状头,前额突出,前顶头部毛发稀疏,眼距宽,眼裂下斜		+			48.5 cm, >3s	+ 2岁时仅会说短词,与人交流少,不会独走
本研究病例2	男	3岁	头颅大,前额突出,下颌尖长,前顶头部毛发稀疏,眼距宽,眼裂下斜		+			52.8 cm, >2s	+ 17个月会走路,2岁叫妈妈, 目前语言表达少
指标	新生儿黄疸	惊厥	中枢神经系统异常	心血管系统异常		泌尿系统异常	其他	基因型
文献[6]	+	+	脑室扩张	-		-	骨龄超前	5~18外显子缺失,其余未覆盖
文献[7] 病例1	-	-	脑影像实质异常	动脉导管及卵圆孔未闭		阴茎短小、肾盂增宽	手足畸形, 低血糖	NSD1基因完全缺失
文献[7] 病例2	+	-	双侧基底节及额叶受损	卵圆孔未闭		左肾积水	喂养困难, 关节挛缩, 腭裂	5号染色体长臂 NSD1基因区域缺失,具体位点不祥
本研究病例1	+	-	胼胝体发育不良, 脑室偏大	动脉导管未闭		-	手指屈曲畸形	NSD1基因完全缺失
本研究病例2	-	+	脑室扩张,脑水肿可能	动脉导管未闭		-	自闭症倾向	新生无义突变,c.1262G>A