PUS3‐related disorder: Report of a novel patient and delineation of the phenotypic spectrum

Abstract

PUS3 encodes the pseudouridylate synthase 3, an enzyme catalyzing the formation of tRNA pseudouridine, which plays a critical role in tRNA structure, function, and stability. Biallelic pathogenic variants of PUS3 have been previously associated with severe intellectual disability, microcephaly, epilepsy, and short stature. We identified a novel homozygous PUS3 frameshift variant in a child with facial dysmorphisms, growth failure, microcephaly, retinal dystrophy, cerebellar hypoplasia, congenital heart defect, and right kidney hypoplasia. This patient further expands the phenotypic spectrum of PUS3-related disorders to include a more severe syndromic presentation.

A young boy with ventricular arrhythmias and thyroid dysgenesis: two genes are not enough?

“…For WES, DNA libraries were enriched using Twist Human Core Exome Kit (Twist Bioscience), and sequenced on a NovasSeq6000 platform (Illumina, San Diego, CA). Bioinformatic analysis was performed as previously reported (14). Annotated variants were filtered and prioritized based on their quality, frequency in the population database gnomAD and predicted On the ECG at 7 years and 3 month of age (Figure 1A), there was a large QRS tachycardia, right bundle branch block and left anterior hemiblock.…”