A Novel Missense Variant in the CHST3 Underlies Spondyloepiphyseal Dysplasia with Congenital Joint Dislocations

Background: Spondyloepiphyseal dysplasia (SED) is characterized by skeletal dysplasia and multiple joint dislocations. SEDs encompass various types, such as SED congenita, SED tarda (SED-T), SED with congenital joint dislocations (SED-CJD), SED stanescu, and SED-T with progressive arthropathy. Methods and Results: In the present study, we clinically and genetically characterized a consanguineous Pakistani family with SED-CJD. The affected member showed large joint dislocation, spinal deformities, and previously unreported facial features. Exome sequencing followed by Sanger sequencing revealed a missense variant, [c.601T>A; p.(Tyr201Asn)], in the CHST3. Conclusion: This study has not only expended the mutation spectrum in the gene CHST3 but also will facilitate diagnosis and genetic counseling of related features in the Pakistani population.