Clinical and molecular characterization of chondrodysplasias in a cohort of Egyptian patients

Skeletal dysplasias (SDs) are a broad and heterogeneous group of genetic disorders primarily affecting bone and collagen development. Diastrophic dysplasia (DTD) is a rare autosomal recessive chondrodysplasia caused by biallelic variants in the SLC26A2 gene. The current study aims to assess the clinical and molecular findings in Egyptian patients with DTD. This study enrolled fifteen patients who were clinically diagnosed with DTD. Exome sequencing identified nine homozygous variants in the SLC26A2 gene across ten patients; five of these variants were novel (p.Cys78Gly, p.Leu132Pro, p.Asp177Tyr, p.Thr546Ala, and p.Leu554Phe), while four had been previously reported. Novel variants were confirmed using Sanger sequencing and were predicted to be disease-causing based on in silico analyses and structural protein modeling. The exome sequencing analysis did not reveal any additional candidate genes that could contribute to the clinical phenotype in patients with negative SLC26A4 causative variants. Our findings expand the spectrum of variants associated with DTD, which may aid in early diagnosis and counseling for affected families. Further studies are needed to confirm computational predictions of novel variants and their consequences in disease mechanisms, and to identify causative genes in the undiagnosed cases.