Silver-Russell综合征患儿1例的遗传变异和生长激素治疗研究  

Analysis of genetic variation and growth hormone response in a patient with Silver- Russell syndrome

作　　者：孙慧慧 张庚 Sun Huihui;Zhang Geng(Department of Pediatrics,Beijing Jishuitan Hospital,Capital Medical University,Beijing 100035,China;Beijing Chigene Translational Medical Research Center Company,Beijing 100176,China)

机构地区：[1]首都医科大学附属北京积水潭医院儿科,北京100035 [2]北京智因东方医学转化研究中心,北京100176

出　　处：《国际遗传学杂志》2024年第2期136-141,共6页International Journal of Genetics

基　　金：北京市医院管理中心"青苗"计划(QML20210403)。

摘　　要：目的分析1例小于胎龄儿患儿的临床表型,明确遗传学病因及核心家系全外显子组测序(trio whole exome sequencing,Trio-WES)在其诊断中的应用价值。方法收集该患儿的临床资料和外周血DNA,该患儿存在重度身材矮小,特殊体征为消瘦、前额大、三角脸、小下颌和双手第5小指弯曲,患儿父母表型正常,采用Trio-WES明确遗传变异,对发现的致病遗传变异进生物信息学分析,明确其致病性。监测生长激素治疗效果。结果本患儿存在7号染色体单亲二倍体(maternal uniparental disomy of chromosome 7,mUPD7),生物信息学分析提示该变异为致病性变异,患儿临床表型符合Silver-Russell综合征。患儿4岁6月开始使用生长激素,经治疗10月,身高由85.7 cm(-5.52SD)改善至94.3cm(-4.61SD)。结论7号染色体单亲二倍体为Silver-Russell综合征患儿的重要发病原因,Trio-WES为发现单亲二倍体的重要遗传学方法。生长激素治疗对改善患儿身高有明确效果。Objective To analyze the phenotype of a patient with small for gestational age(SGA),further to identify the genetic variation,and to explore the application of trio whole exome sequencing(Trio-WES)in SGA.Methods The clinical data and peripheral blood DNA of the proband were collected.The proband complained of severe short stature.His clinical features included slim build,wide forehead,triangular face,narrow chin and two fifth finger clinodactyly.His parents were both normal.Trio-WES was applied to identify the genetic variant,which was further confirmed by bioinformatics analysis.The height increase was monitored after growth hormone treatment.Results Maternal uniparental disomy of chromosome 7(mUPD7)was identified in the affected proband.Bioinformatics analysis suggested the variant was pathogenic.Clinical manifestations of the proband were accordant with Silver-Russell syndrome.At age of 4 years and 6 months,her height was 85.7 cm(-5.52SD)and growth hormone was initiated.After 10 months’treatment,her height was improved to 94.30 cm(-4.61SD).Conclusions mUPD7 was the pathogenic variation of the patient with SGA.Trio-WES is an important approach to identify UPD.The patient had effective height increase with growth hormone therapy.

关 键 词：Silver-Russell综合征 核心家系全外显子组测序 单亲二倍体 小于胎龄儿 生长激素 

分 类 号：R725.9[医药卫生—儿科]