FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay / 대한소아신경학회지

ABSTRACT

Most cases of microcephaly with growth failure and developmental delay have a genetic or metabolic etiology. Whole-exome sequencing (WES) has uncovered many causative genes and has also broadened their phenotypic spectrum. The present study applied WES to a boy with microcephaly, growth failure, developmental delay, seizures and atopic dermatitis, which reveal an unexpected frame-shift mutation (c.1248_1253delinsCT, NM_014009.3; p.Lys416Asnfs, NP_054728.2) in the forkhead box P3 gene (FOXP3). Mutations of this gene are known to result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Mutation of FOXP3 was reverified by Sanger sequencing in the proband and his carrier mother. Flow-cytometry expression study of FOXP3 in peripheral white blood cells showed that the mean fluorescence intensity of FOXP3 was lower in the proband than in a normal control. We report a mild form of IPEX syndrome without chronic protracted diarrhea or major infections, instead presenting with proportional microcephaly, growth failure, developmental delay, seizures and atopic dermatitis.