Marie Materna,et al.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression.Low circulating naive αβ T cell counts at birth persisted over time,with normal memory αβ and high γδ T cell counts.Their TCRα repertoire was biased,which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development.Only a minority of these individuals were sick,with infection,lymphoproliferation,and/or autoimmunity.We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant.They had normal circulating naive αβ T cell counts but high γδ T cell counts.Although residual pre-TCRα expression drove the differentiation of more αβ T cells,autoimmune conditions were more frequent in these patients compared with the general population.