WDFY3 loss-of-function leads to increased proliferation and altered differentiation of neuronal cells underlying the haploinsufficient human phenotype

Neurodevelopmental disorders (NDD) are poorly understood, and late diagnosis and interventions result in a high burden for the society and health system. WD Repeat and FYVE Domain Containing 3 (WDFY3) encodes for the autophagy adaptor protein ALFY. Loss-of-function (lof) variants in WDFY3 result in a monogenic condition characterized by mild to moderate developmental delay, neuropsychiatric disorders, and altered brain size. We present a comprehensive description of lof WDFY3-associated phenotypes in the largest cohort of patients to date (n = 26).