一例Donohue综合征新生儿的基因变异分析

Analysis of pathogenic gene variant in a patient with neonatal Donohue syndrome

目的从分子水平明确1例疑似为Donohue综合征的新生儿的诊断。方法对患儿进行全外显子组测序(whole exome sequencing,WES),之后用Sanger测序和实时定量PCR对候选变异进行验证。结果WES检出患儿携带INSR基因的两处杂合变异,即c・3258+4(IVS17)A>G和第2外显子缺失,其中前者为新发现的变异。家系分析显示上述变异分别遗传自患儿的母亲和父亲,并经Sanger测序和实时定量PCR证实。结论INSR基因c.3258+4(IVS17)A>G和第2外显子杂合缺失所构成的复合杂合变异可能是导致患儿发病的原因。

Objective To explore the genetic basis for a newborn infant suspected with Donohue syndrome.Methods Whole exome sequencing(WES)was used to screen potential variants in the child.Suspected variants were validated through Sanger sequencing and real-time PCR.Results The child was found to carry two heterozygous variants in the INSR gene,including c.3258+4(IVS17)A>G and deletion of exon 2,which were respectively inherited from her mother and father.Conclusion The compound heterozygous variants of the INSR gene probably underlie the disease in this patient.