摘要
目的对5例经基因确诊的DiGeorge综合征患儿的临床表型、诊断及治疗过程进行回顾性分析及文献复习。方法收集整理本院儿科收治的5例确诊为DiGeorge综合征患儿的临床资料,基于二代基因测序(next generation sequencing,NGS)技术的基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)对患儿进行遗传学病因诊断,重点对比5例患儿之间的临床表型与基因型的对应关系。结果本研究收集的5例患儿就诊年龄均小于6个月,随访时间为2个多月~1年,首诊症状多为抽搐和(或)反复感染,均存在不同程度的生长迟缓,伴或不伴特殊面容、癫痫、先天性心脏病等,血离子钙水平相似均显示低钙血症,但临床发生抽搐的频率和严重程度不一。5例患儿均检测到染色体22q11.21的拷贝数变异,缺失片段在2.56~2.6 Mb之间,与Decipher数据库收录的DiGeorge综合征缺失区域(chr22:19009792-21452445)大部分重合。1例提示为新生变异,其余4例父母未做CNV-seq验证。结论DiGeorge综合征存在较大临床异质性,基于NGS的CNV-seq技术不仅有利于精准的遗传学病因诊断,还有助于深入认识遗传性综合征临床表型与基因型的对应关系,提高临床医生对其认识,免误诊漏诊。
Objective To identify the clinical phenotypes,diagnosis,and treatment of five children with DiGeorge syndrome finally diagnosed by gene,with review of the literature.Methods The clinical data of five children with DiGeorge syndrome admitted to our hospital were collected and sorted out.Copy number variation sequencing(CNV-seq)based on next generation sequencing(NGS)technology was used to diagnose the genetic etiology of the children.The relationship between phenotypes and genotype among these five children were emphatically compared.Results The five children collected in this study were all younger than 6 months.The course of the disease was more than 2 months to 1 year.Most of the first symptoms were convulsions and/or repeated infection.All of them had different degrees of growth retardation,with or without special facial features,epilepsy,congenital heart disease,etc.The similar blood ionized calcium levels revealed hypocalcemia,but the frequency and severity of convulsions were different.The copy number variation of chromosome 22q11.21 was detected in all these five children,and the deletion fragment was between 2.56-2.6 Mb,which was mostly coincident with the classical deletion region of DiGeorge syndrome(chr22:19009792-21452445)recorded in Decipher database.One case was suggested to be a novel mutation,and the rest were of unknown origin.Conclusions DiGeorge syndrome has great clinical heterogeneity.CNV-seq based on NGS technology is not only conducive to accurate genetic etiological diagnosis,but also helpful for understanding the corresponding relationship between clinical phenotype and genotype of hereditary syndrome,improving clinicians′understanding and avoiding misdiagnosis.
作者
吴静
孟歌
徐千雅
韩素鸽
侯雅勤
白莹
马威
孔惠敏
孔祥东
Wu Jing;Meng Ge;Xu Qianya;Han Suge;Hou Yaqin;Bai Ying;Ma Wei;Kong Huimin;Kong Xiangdong(Department of Pediatric Internal Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Neonatology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2020年第6期485-491,共7页
Chinese Journal of Endocrinology and Metabolism
基金
国家自然科学基金青年项目(81300685、81501851)
河南省教育厅高等学校重点科研项目(19B320032)
河南省医学科技攻关计划项目(201702003)。