Evaluation of the Impact of a PUS7 Gene Variant on Dental Development: A Rare Case Report

Pseudouridylation, the enzymatic isomerization of uridine to pseudouridine, is a widespread posttranscriptional RNA modification that contributes to RNA stability and regulation of gene expression. The PUS7 gene encodes pseudouridine synthase 7 (PUS7), and its biallelic pathogenic variants have been associated with a syndromic neurodevelopmental disorder characterized by intellectual disability, microcephaly, behavioral abnormalities, growth retardation, and facial dysmorphism. Recent data indicate that PUS7 interacts with SIRT1, a key regulator of the Wnt/β-catenin signaling pathway, suggesting that PUS7 dysfunction may indirectly influence odontogenesis.

We report a boy patient born to consanguineous parents, in whom exome sequencing identified a novel homozygous truncating variant in PUS7 (NM_019042.5): c.1097_1098del p.(Leu366GLnfs*7). Clinical assessment revealed neurodevelopmental delay, facial dysmorphism, and dental anomalies. At 28 months of age, the mandibular primary lateral incisors (72 and 82) were absent, whereas the mandibular central incisors exhibited a conical morphology.

Although dental anomalies have been reported in PUS7-related disorders, the abnormalities may be overlooked in children with neuromotor delay. Conical teeth appear to be a more distinctive and clinically recognizable feature, as observed in our patient. Further studies are needed to clarify the role of PUS7 variants in dental development and genotype-phenotype correlations.