一例5q14.3微缺失综合征患儿的临床表型及遗传学分析

Clinical phenotype and genetic analysis of a case of 5q14.3 microdeletion syndrome

目的探讨1例5q14.3微缺失综合征患儿的临床表型和遗传学病因。方法应用全外显子组测序技术(whole exome sequencing,WES)及低深度全基因组测序技术(low-coverage massively parallel copy number variation sequencing,CNV-seq)对患儿进行可能致病变异及染色体拷贝数变异(copy number variations,CNVs)分析,对检测到的微小基因组拷贝数异常区域通过实时荧光定量PCR进行验证。结果患儿主要临床表现包括全面性发育迟缓、癫痫、特殊面容、肌张力低下。WES检测提示患儿chr5:86564268-88119605区可能存在杂合缺失。CNV-seq检测提示患儿5q14.3区存在大小为4.76 Mb的杂合缺失。对缺失区域内的MEF2C基因和RASA1基因应用实时荧光定量PCR进行验证,结果显示MEF2C基因和RASA1基因杂合缺失,与测序结果相符。结论通过临床及基因测序分析,患儿被诊断为5q14.3微缺失综合征。该患儿的MEF2C基因单倍体不足可能是导致5q14.3微缺失综合征神经精神发育障碍相关临床表型的主要原因。

Objective To explore the clinical features and genetic characteristics of a child with 5q14.3 microdeletion syndrome.Methods Whole exome sequencing(WES)and low-coverage massively parallel copy number variation sequencing(CNV-seq)were used to determine the potentially pathogenic variants as well as the copy number variations(CNVs).Candidate CNVs were verified by real-time fluorescence quantitative PCR.Results The patient presented with psychomotor retardation,epilepsy,peculiar face and hypotonia.The results of WES suggested that the patient carried a heterozygous deletion for chr5:86564268-88119605.CNV-seq indicated that he has carried a heterozygous deletion of 4.76 Mb heterozygous deletion on chromosome 5q14.3.The MEF2C gene and RASA1 genein the deletion area were verified by real-time fluorescence quantitative PCR.The results showed that the MEF2C gene and RASA1 gene were heterozygous deletion,which was consistent with the sequencing results.Conclusion The child was diagnosed with 5q14.3 microdeletion syndrome.Haploinsufficiency of the MEF2C gene may underlie the manifestations of 5q14.3 microdeletion syndrome.