Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay

A homozygous mutation in the FTO gene encoding a 2-oxoglutarate dependent oxygenase was previously identified as the cause of a syndrome characterized by growth retardation and multiple malformations. No other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. We investigated a 21-month-old girl who presented with growth retardation and global developmental delay. We performed targeted next-generation sequencing of 4813 clinically relevant genes in the patient and her parents and identified a novel FTO homozygous missense substitution p.(Ser319Phe) in the patient. Biochemical studies reveal that this substitution reduces the catalytic activity of the FTO protein. Our findings reinforces the hypothesis that homozygous mutations in FTO can lead to rare growth retardation and developmental delay syndrome and further support the proposal that FTO plays an important role in early development of the human central nervous system. (By Dr. Hussein Daoud, http://jmg.bmj.com/content/early/2015/09/16/jmedgenet-2015-103399 )