Novel Variants in PUS7 Associated With Intellectual Disability and Growth Retardation: Expanding the Clinical Spectrum in 13 Patients

Pathogenic PUS7 variants, pseudouridine synthase, impaired RNA pseudouridylation, transcriptomic instability

13 new patients with pathogenic PUS7 variants are described, extending the worldwide cohort to approximately 29 cases. PUS7 encodes a pseudouridine synthase involved in post-transcriptional RNA modification; its variants cause a syndrome with marked intellectual disability, growth and weight retardation, microcephaly, and self-injurious behaviors. The cohort refines genotype-phenotype correlations: truncating variants cause the most severe forms, with variable expressivity for missense variants. PUS7 is now among the best characterized NDD genes linked to the pseudouridylation pathway.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

PUS7 illustrates the importance of RNA pseudouridylation in neurodevelopment, a mechanism underrepresented in standard genetic panels. With approximately 29 total cases, the cohort now reaches the robustness threshold for systematic inclusion in NDD panels, particularly for the combination of ID + microcephaly + self-injurious behavior.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 8/10