Bayanova Mirgul, Abilova Aigerim, Rakhimzhanova Marzhan, Bazenova Assiya, Nazarova Lyazzat, Malik Dias, Tanko Naanlep Matthew, Altaeva Nursulu, Bolatov Aidos
"University Medical Center" Corporate Fund, Turan Ave. 38, 010000, Astana, Kazakhstan.
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, 010000, Kazakhstan.
Sci Rep. 2025 Apr 2;15(1):11223. doi: 10.1038/s41598-025-95877-z.
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.
本研究调查了哈萨克斯坦儿科人群成骨不全症（OI）的基因图谱和表型谱，重点关注2021年7月至2023年6月在“大学医学中心”企业基金接受诊断和治疗的40名儿童。在哈萨克斯坦阿斯塔纳的“纳扎尔巴耶夫大学国家实验室”对22名参与者进行了全基因组测序，在私人实验室对18名参与者进行了全外显子组测序，以进行基因分析。在35例（87.5%）中发现了具有临床意义的基因变异。在24例（68.6%）中检测到COL1A1和COL1A2基因的突变，其中5种变异是首次描述。在罕见的OI病例中，鉴定出IFITM5（n = 2）、SERPINF1（n = 7）和SERPINH1（n = 1）基因的变异。同时，7例无亲缘关系的病例在SERPINF1基因中具有相同的变异（c.907C>T，其中6例为纯合子，1例为复合杂合子状态），2例在IFITM1基因中具有相同变异（c.-14C>T）。在17%的病例中鉴定出了新的致病变异，且发现胶原蛋白缺陷的比例较高。本研究确定的常染色体隐性遗传OI的相对较高比例应在哈萨克斯坦及中亚国家的人群水平上进行调查。此外，本研究描述了基因型与表型的相关性，补充并扩展了关于OI的现有知识。
