FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay.

Cho,  Hwa Jin; Choi,  Ga Eun; Kim,  Young Ok; Park,  Chungoo; Yang,  Eun Mi; Kim,  Chan Jong; Kim,  Myeong Kyu; Shin,  Myung Geun; Woo,  Young Jong

doi:2017.25.4.266

Ann Child Neurol > Volume 25(4); 2017 > Article

Case Report

Journal of the Korean Child Neurology Society 2017;25(4):266-270.
DOI: https://doi.org/10.26815/jkcns.2017.25.4.266 Published online December 30, 2017.

FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay.

Hwa Jin Cho, Ga Eun Choi, Young Ok Kim, Chungoo Park, Eun Mi Yang, Chan Jong Kim, Myeong Kyu Kim, Myung Geun Shin, Young Jong Woo

¹Department of Pediatrics, Chonnam National University Medical School, Gwangju, Korea. ik052@jnu.ac.kr
²School of Biological Sciences and Technology, Chonnam National University, Gwangju, Korea.
³Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
⁴Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

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.

Key Words: Microcephaly, Failure to thrive, Growth and development, Gene, Seizures, Atopic dermatitis