以先天性甲状腺功能减退为表现的14q12q13.3微缺失综合征患儿1例的临床及遗传学分析

Clinical phenotype and genetic analysis of a child with 14q12q13 microdeletion syndrome manifesting as congenital hypothyroidism

目的分析1例以先天性甲状腺功能减退症(CH)为表现的14q12q13.3微缺失综合征患儿的临床表型与遗传学病因。方法以1例因先天性甲状腺功能减退就诊于临沂市人民医院的新生儿作为研究对象,对其进行全外显子组测序(WES)、深度基因组拷贝数变异(CNV)和染色体微阵列分析(CMA),分析其临床资料并进行文献复习。结果患儿于新生儿期起病,主要表现为特殊面容、外阴水肿、肌张力低下、精神运动发育迟缓、反复呼吸道感染伴喉喘鸣和喂养困难等,实验室检测显示甲状腺功能减退。WES和深度基因组CNV分析检测提示患儿染色体14q12q13.3区可能存在拷贝数缺失,CMA证实其14q12q13.3区(3264959536769800)存在4.12 Mb的片段缺失,共涉及22个基因,包含CH的致病基因NKX2-1,患儿父母均未发现同样的片段缺失。结论综合其临床表型及基因检测的结果,确诊患儿为14q12q13.3微缺失综合征。

Objective To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism(CH).Methods Whole exome sequencing(WES),copy number variation(CNV)sequencing and chromosomal microarray analysis(CMA)were carried out for a newborn infant who had presented at Linyi People′s Hospital for CH.Clinical data of the child was analyzed,in addition with a literature review.Results The main characteristics of the newborn infant had included peculiar face,vulvar edema,hypotonia,psychomotor retardation,recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties.Laboratory test indicated hypothyroidism.WES suggested a CNV deletion on chromosome 14q12q13.CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3(32649595_36769800),which has encompassed 22 genes including NKX2-1,the pathogenic gene for CH.The same deletion was found in neither of her parents.Conclusion Through the analysis of clinical phenotype and genetic variant,the child was diagnosed with 14q12q13.3 microdeletion syndrome.