新生儿CHARGE综合征5例临床及基因变异分析

Analysis of clinical features and gene mutations in five neonates with CHARGE syndrome

目的分析5例诊断为新生儿CHARGE综合征患儿的临床特征及基因变异特点,明确死亡患儿的遗传学病因。方法收集5例患儿的临床资料,应用高通量测序技术对5例疑诊CHARGE综合征患儿进行检测,利用Sanger测序技术对可疑位点和核心家系成员进行验证。结果5例患儿均存在结构畸形合并喂养困难(均排除鼻后孔闭锁),其中2例出现歪嘴哭。3例患儿合并鼻腔狭窄或者上气道塌陷综合征,因治疗效果差,不能撤离呼吸机最终死亡;1例患儿因家属放弃治疗死于家中;1例目前随访中。家系1为CHD7基因c.478 del(Y160Tfs*51)移码变异,家系2为CHD7基因c.5428C>T(P.R 1810*)无义变异,家系3为CHD7基因c.6292C>T(P.R 2098*)无义变异,家系4为CHD7基因c.4317 delA(p.Q 1440 S fs*3)移码变异,家系5为CHD7基因c.469C>T(P.R157*)无义变异。5个家系的父母均未携带相应的变异,均为新发变异。其中家系4的CHD7基因c.4317 delA为未报道的新变异。结论CHD7基因变异可能为5例患儿的致病原因,其中4例患儿死亡的遗传学病因可能为CHD7基因变异导致的系统畸形。对于类似多发畸形患儿临床诊断的同时应积极完善基因检测明确遗传学诊断,以提高对该病的认识。

Objective To analyze the clinical features and gene variation characteristics of 5 children diagnosed with neonatal CHARGE syndrome,and to identify the genetic etiology of the deaths.Methods The clinical data of 5 children were collected.High-throughput sequencing technology was used to detect 5 children with suspected CHARGE syndrome,and Sanger sequencing technology was used to verify the suspicious loci and core family members.Results Clinical features of 5 cases:structural deformity combined with feeding difficulties(both excluded posterior nasal atresia),2 children with crooked mouth crying,3 children with nasal cavity stenosis or upper airway collapse syndrome who,due to poor treatment effect,could not be removed from the ventilator and eventually died,1 patient's family members gave up treatment and died at home;1 patient is currently being followed up.Family 1 had a frameshift variant of the CHD7 gene c.478 del(Y 160 Tfs*51),family 2 had a nonsense variant of the CHD7 gene c.5428 C>T(P.R 1810*),and family 3 had a nonsense variant of the CHD7 gene c.6292 C>T(P.R 2098*),family 4 had a frameshift variant of the CHD7 gene c.4317 delA(p.Q 1440 S fs*3),family 5 had a nonsense variant of the CHD7 gene c.469 C>T(P.R 157*).The parents of the 5 families did not carry the corresponding variats,and the varians were all de novo.The c.4317delA in family 4 was previously unreported.Conclusion The CHD7 gene mutation may be the pathogenic cause of 5 cases.The genetic cause of death in 4 cases may be system malformation caused by CHD7 gene mutation;for the clinical diagnosis of children with similar multiple malformations,the genetic testing should be actively improved to make the diagnosis clear,so as to improve the clinician's understanding of the disease.