Expanding the Phenotypic Spectrum of FTO-Related Developmental Disorder Caused by Biallelic Variants in FTO.

Abstract

Fat Mass and Obesity-Associated (FTO) gene encodes a versatile RNA-modifying enzyme that regulates gene expression, RNA processing, and protein synthesis by demethylating different RNA substrates. FTO has a wide range of effects on mammalian physiological functions in regulating fat mass, adipogenesis, and energy homeostasis. Bi-allelic variants in FTO cause growth failure, developmental delay, and facial dysmorphism. Earlier reported individuals carried variants at critical catalytic sites and had severe developmental phenotypes with early childhood lethality. We report 13 additional individuals from nine families with variable prenatal and postnatal phenotypes with variants in FTO (NM_001080432.3). We add a presumably founder variant c.608 T>C in seven individuals from four Indian families with milder clinical and neuroimaging findings compared to earlier reports. We reviewed genotype-phenotypes of the current series and previous individuals with FTO-related developmental disorders. We also document the prenatal phenotypes of FTO variants, thereby expanding the spectrum of FTO-related developmental anomalies.

Abstract as supplied by the indexing source. © the authors / publisher.