İskelet Tutulumunun Olduğu Siliyopatilerin Klinik ve Moleküler Özellikleri ile Oksidatif Stres Parametrelerinin Değerlendirilmesi

Abstract

Ciliopathies encompass a broad spectrum caused by variants in genes associated with ciliogenesis and ciliary trafficking. Among these, skeletal ciliopathies with predominant skeletal involvement are classified as a subgroup of genetic skeletal disorders. A total of 20 patients with a clinical preliminary diagnosis of skeletal ciliopathy who presented to the outpatient clinic of Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Genetic Diseases, were included in the study. The clinical and radiographic findings of the patients were reviewed, and whole exome sequencing was performed to elucidate the molecular etiology. Molecular etiology was identified in 16 (80%) of the patients, while no causal variants were detected in four (20%). Based on clinical and molecular findings, six patients were diagnosed with Ellis-van Creveld syndrome, six with oral-facial-digital syndrome, five with short-rib thoracic dysplasia, one with Meckel-Gruber syndrome, one with cranioectodermal dysplasia, and one with an undefined ciliopathy with skeletal involvement. The most frequently detected variants were in the EVC gene, followed by DYNC2H1. Among the identified variants, nine novel variants were described in the EVC, EVC2, DYNC2H1, FAM149B1, KIAA0586, IFT80, and WDR35 genes. Oxidative stress parameters were found to be elevated in the skeletal ciliopathy patient group compared to the control group; however, statistical analyses did not show a significant difference. This study has detailed the clinical, radiographic, and molecular characteristics of skeletal ciliopathies and contributed to the expansion of the mutational spectrum.