Abstract
This study investigates the genetic landscape and phenotypic spectrum of osteogenesis imperfecta (OI) in the Kazakhstani pediatric population, focusing on 40 children diagnosed and treated at the "University Medical Center" Corporate Fund from July 2021 to June 2023. Genetic analysis was conducted using whole-genome sequencing for 22 participants at the "National Laboratory Astana" (Nazarbayev University, Astana, Kazakhstan) and whole-exome sequencing for 18 participants in private laboratories. Clinically significant genetic variants were found in 35 cases (87.5%). Mutations in the COL1A1 and COL1A2 genes were detected in 24 cases (68.6%), among them 5 variants were described for the first time. Among the rare cases of OI, variants in the IFITM5 (n = 2), SERPINF1 (n = 7), and SERPINH1 (n = 1) genes were identified. At the same time, seven unrelated cases had identical variants in the SERPINF1 gene (c.907C > T, 6 of which in the homozygous and 1 in the compound heterozygous state) and two cases in the IFITM1 gene (c.-14C > T). Novel disease-causing variants were identified in 17% of cases, and a higher proportion of collagen defects were seen. The relatively high proportion of autosomal recessive inherited OI determined in the current study should be investigated at the population level in Kazakhstan and in the countries of Central Asia. Moreover, this study described the genotype-phenotype correlation, which complements and expands the existing knowledge about the OI.