A Single-Center Retrospective Cohort Study of Genotype–Phenotype Correlation of Osteogenesis Imperfecta in UAE

Abstract Background Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by skeletal fragility. Patients with OI suffer recurrent fractures, limb deformities, and kyphoscoliosis. Multiple extraskeletal manifestations might also be present. Autosomal dominant variants in the COL1A1 or COL1A2 genes account for approximately 90% of cases. Objective The aim of the study was to describe the variant spectrum and genotype–phenotype correlations in patients with OI seen in Tawam Hospital in the UAE. Methods The authors conducted a retrospective chart review for all patients with OI assessed by geneticists at Tawam Hospital from January 2010 to December 2021. They retrieved each patient's baseline characteristics, detailed history and physical examination, laboratory, imaging, and genetic results. Results A total of 40 patients with OI were found and included in this study. The majority (80%) were Emirati, and 57.5% were females. Consanguinity was documented in 24.3%. Thirty-seven patients (92.5%) had positive molecular testing; 28 patients (75.7%) had an autosomal dominant inheritance, and 9 patients (24.3%) had an autosomal recessive inheritance. The majority had missense variants. Four variants were novel. A high prevalence of pathogenic variants in the COL1A1 gene (57%) was found. Patients with variants in the LEPRE1 gene had early and severe phenotypes, while patients with variants in the TMEM38B gene had variable presentations. The majority of patients (85%) had skeletal phenotypes: fractures, bone deformity, scoliosis, and osteopenia. Extraskeletal phenotypes included blue sclera, dentinogenesis imperfecta, hearing loss, and dysmorphic features. Conclusion This study reports the genotype–phenotype correlation of OI patients from the UAE. A high prevalence of pathogenic variants in the COL1A1 gene with OI type IV phenotype was found. Further multicenter more extensive studies are recommended.