Genotype–phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta

Abstract

Purpose To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts. Methods A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts. Results A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts. Conclusion The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.

Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants

“…As shown in previous studies, OI patients with biallelic variants often had severe phenotypes ( 4 ). OI type VII is an autosomal recessive form of OI caused by CRTAP mutations, which can lead to loss of the prolyl-3-hydroxylase complex and disturb the architecture of the type I collagen structure ( 6 ).…”

“…Mutations in COL1A1 or COL1A2 lead to autosomal dominant OI through inducing quantitative deficiencies or structural defects of type I collagen ( 3 ). The remaining OI cases are caused by mutations in a variety of other genes, and patients with the recessive form of OI usually show more severe phenotypes, including more fractures, more severe skeletal deformities, shorter stature, and poorer mobility ( 4 ).…”

Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients

“…The COL1A1 and COL1A2 mutations were among the most commonly reported. Other findings included the correlation between genotype and phenotype, depending on the mutation and the protein modification caused [47]. A group of investigators from Estonia, Vietnam, and Ukraine showed that 82 (56.16%) patients of all the 146 examined cases revealed pathogenic de novo variants.…”