Genetic and clinical features of 3 cases of neonatal diabetes mellitus caused by forkhead box P3 gene mutation

Objective To elucidate the clinical characteristics and genotype-phenotype relationships of Chinese patients with neonatal diabetes mellitus (NDM) caused by forkhead box P3 (FOXP3) gene mutations (FOXP3-NDM). Methods A total of 50 suspected patients with NDM were recruited from Peking Union Medical College Hospital. After the detailed collection of clinical information, target sequencing of 21 known causative genes of NDM were performed for molecular genetic diagnosis. Results Three patients with FOXP3-NDM were identified, separately carrying FOXP3 p.R312H, p.V408M, and p.P133L hemizygous mutations. All these 3 patients showed simple permanent NDM, without other common manifestations of IPEX syndrome until 9-12 years old. And they only need insulin therapy. However, all the foreign reported cases presented multiple autoimmune diseases besides NDM, and needed immunosuppressive therapy, even with the same mutation. Conclusion This is the first report of Chinese FOXP3-NDM patients, which showed totally different clinical phenotypes from foreign reported cases. The underlying molecular mechanism remains to be further studied. Key words: Diabetes mellitus; Infant, newborn; Forkhead box P3; IPEX syndrome