Commentary on UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression

We read with great interest the publication by Wang et al,1 which described three unrelated children under 5 years of age carrying genetic variants likely to induce UBTF (Upstream Binding Transcription Factor) haploinsufficiency. These children presented a phenotype characterised by intellectual disabilities, social challenges, and developmental delays in language and gross motor skills. The phenotype described by Wang et al is strikingly different from that observed in patients carrying the recurrent de novo p.(Glu210Lys) variant in UBTF, which causes childhood-onset neurodegeneration with brain atrophy (CONDBA, MIM 617672) through a gain of function mechanism.2 3