Expanding the clinical spectrum of RNU4ATAC-opathies: more frequent and diverse than assumed

Biallelic variants in the noncoding minor spliceosomal gene *RNU4ATAC* causing an expanded syndrome spectrum including autoimmune manifestations

A French and European multicenter study collected data from 69 participants with biallelic RNU4ATAC variants, identifying 18 novel pathogenic variants. Attenuated or atypical presentations were reported in a significant proportion, and autoimmune/inflammatory manifestations were detected in nearly half of participants — a previously unrecognized association. Computer-assisted facial analysis revealed a specific dysmorphic pattern. Integration with 109 published cases proposes a new classification based on two main axes: immunodeficiency and microcephalic primordial dwarfism.

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The predominance of classic Taybi-Linder forms in the literature was likely a publication bias. Autoimmune manifestations in nearly half of patients reconfigure the clinical picture and open therapeutic avenues. These diseases are likely underdiagnosed, particularly in their pauci-symptomatic forms.