Clinical Features Of A Case With Neonatal CHARGE Syndrome And Fuctional Verification Of Novel Mutation In CHD7

Objective:CHARGE syndrome(CS)is an autosomal dominant disorder that often presents with multiple organ malformations,and the diagnosis is mainly based on clinical symptoms,and differential diagnosis often requires rich clinical experience due to the overlap between clinical appearance and other syndromes.In this study,we analyzed the clinical data of a case of neonatal CHARGE syndrome,and a genome-wide report revealed a novel mutation site c.3378 + 5G > T in the CHD7 gene,which was analyzed using Minigene technology to verify the pathogenic mechanism of this mutation for the disease.Methods : The clinical data of a neonate with CHARGE syndrome admitted to the department of neonatology of Wuhan Children’s Hospital were collected,including general data,maternal pregnancymessage,clinical manifestations,auxiliary examinations.Exome sequencing of peripheral blood confirmed a novel mutation,and minigene technology were performed for functional verification additionly.Results:The neonate was a G2P1G37+3 boy,admitted to the Department of Neonatology of other hospital and our hospital with the presentation of shortness of breath after birth.The main clinical manifestations included coloboma;bilateral testicular dysplasia;cardiac malformation included patent ductus arteriosus,coarctation of aorta,mild aortic valve stenosis,aortic dysplasia,atrial septal defect;ear anomalies;hand malformation;dysphagia;brain atrophy,etc.,and the boy was clinically diagnosed as CHARGE syndrome.Whole genome sequencing revealed a novel mutation site c.3378 + 5G > T in the CHD7 gene.Further,minigene technology,which was used for vitro functional validation of the alternative splicing effect,was performed,and revealed that the c.3378 + 5G > T mutation caused aberrant splicing of the pre-m RNA,resulting in exon13 loss and intron13 partial base(16 bp)retention in the m RNA.Combined with the typical clinical manifestations,abnormal gene mutations and in vitro validation results,CHD7: c.3378 + 5G > T was preliminarily confirmed as the causative locus in this child.Conclusion :The novel mutation c.3378 + 5G > T of CHD7 is the pathogenic locus of CHARGE syndrome,which enriches the current phenotype and provides the basis for the early diagnosis and targeted therapy of disease.