Clin Genet. 2025 Jun 2. doi: 10.1111/cge.14779. Online ahead of print.
ABSTRACT
This study reports a skeletal disorder marked by facial dysmorphism and a distinct oro-dental phenotype including premaxillary and gingival overgrowth and hypercementosis. Whole-exome sequencing identified a homozygous missense variant in ENPP5 (c.173G>T; p.Gly58Val), affecting a conserved glycine residue predicted to be within a putative active binding site of the ENPP5 protein. In mice, RNA-seq and immunofluorescence confirmed Enpp5 expression in functional osteoblasts of the maxilla and mandible, periodontal ligament, odontoblasts, and ameloblasts. RT-qPCR confirmed region-specific expression, with higher Enpp5 expression in premaxillary-maxillary bones compared to the tibia, suggesting site-dependent functional roles. This report links, for the first time, a biallelic ENPP5 variant to a novel syndrome involving premaxillary development, bone and cementum growth, highlighting the need for further functional and clinical investigation.
PMID:40457511 | DOI:10.1111/cge.14779
