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

Pseudouridylation is a frequent post-transcriptional modification resulting in uridine isomerization in 5-ribosyluracil, also called pseudouridine. This mechanism leads to RNA stability with an increase in base-stacking and the creation of hydrogen bonds. Recently, papers reported that variants in PUS7 in 16 patients were involved in marked growth retardation with microcephaly, associated with intellectual disability and behavioral issues such as self-injurious and aggressive behavior. Through Genematcher, we initiated a collaboration to describe a new cohort of PUS7 patients. In total, we report 13 new cases carrying 15 new variants. This cohort further expands the phenotypic spectrum associated with PUS7-related syndromes, allowing for improved genotype-phenotype correlations and ultimately better healthcare for affected individuals and their families.