Screening For FOXP3 Gene Mutations In Immune Dysregulation,Polyendocrinopathy,Enteropathy,X-linked Syndrome

Objective:To report on two cases affected with Immune dysregulation,polyendocrinopathy,enteropathy,X-linked syndrome(IPEX).Methods:1.Collect clinical data of children.(1)Case 1:a 4 months old boy was in hospital due to "4 months of hyperglycemia".He had neonatal diabetes mellitus in his neonate period and treated with insulin.Local hospitals diagnose neonatal diabetes mellitus.Postnatal symptoms of persistent diarrhea and recurrent eczema.then,rashes,diarrhea and pneumonia were re-occurred with him.Pneumonia was improved with anti-infection and intravenous gamma globulin therapy,and his blood sugar was stabilized.then he left hospital.One month later,followed up by telephone,we learned the child had died.(2)Case 2,a 6 days old by was enrolled for "Eat less,move less for one day".He had neonatal diabetes,ketoacidosis,hyperkalemia,hypernatremia and hypertonic dehydration.After admission,patients were given volume expansion rehydration,insulin hypoglycemia,liver protection and anti-infection treatment.After stable illness,diarrhea was evident when fed with regular formula milk.After one month of postnatal blood sugar was stable,the patient was discharged from hospital.Call back to inform that eczema was obvious after discharge,and died of severe pneumonia at the age of 2 months after giving up treatment.2.Gene mutation detection:During hospitalization,with the informed consent of the parents,the peripheral venous blood of the children and their parents were extracted and mixed in the EDTA anticoagulant tube.The whole blood DNA was extracted by genomic DNA extraction kit and sent to Beijing Deyi Oriental Translational Medical Research Center for FOXP3 gene detection.The newly discovered mutation sites were validated with 100 unrelated healthy children as controls,and the mutation function was predicted by bioinformatics software.Results:Both infants had onset of the disease during neonatal period,and manifested insulin-dependent diabetes mellitus,persistent diarrhea,eczema and malnutrition.In casel,a novel splice site mutation was identified in intron(c.967+3A>T)of the FOXP3 gene,for which his mother was a carrier.For case 2,a missense mutation(c.1150G>A)was found in exon 11 of the FOXP3 gene,for which his mother was also a carrier.The IVS9 c.967+3A>T mutation was not detected among the 100 healthy controls.As predicted with Human Splicing Finder software,the c.967+3A>T mutation may influence the splicing of mRNA and affect the function of protein.Conclusion:Both cases had typical clinical manifestation of the IPEX syndrome.Among whom a novel splice site mutation in intron(c.967+3A>T)and a missense heterozygous mutation in exon 12(c.1150G>A)of the FOXP3 gene were identified.The clinical manifestation of the IPEX syndrome may be variable and the mortality is high.FOXP3 gene sequencing is recommended when insulin-dependent diabetes mellitus is diagnosed during the neonatal period.