title: Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta.
abstract: The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI.
  
  
  
  Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant identification was performed with Mutation Surveyor DNA variant analysis software. Prediction of the pathogenicity of mutations was conducted using Alamut Visual software. The presence of variants was checked against Dalgleish's osteogenesis imperfecta mutation database.
  
  
  
  The sample consisted of 91 unrelated osteogenesis imperfecta patients. We identified 54 patients with COL1A1/2 pathogenic variants; 33 with COL1A1 and 21 with COL1A2. Two patients had multiple pathogenic variants. Seventeen novel COL1A1 and 10 novel COL1A2 variants were identified. The majority of identified COL1A1/2 pathogenic variants occurred in a glycine substitution (36/56, 64.3 %), usually serine (23/36, 63.9 %). We found two pathogenic variants of the COL1A1 gene c.2461G > A (p.Gly821Ser) in four unrelated patients and one, c.2005G > A (p.Ala669Thr), in two unrelated patients.
  
  
  
  Our data showed a lower number of collagen OI pathogenic variants in Vietnamese patients compared to reported rates for Asian populations. The OI mutational profile of the Vietnamese population is unique and related to the presence of a high number of recessive mutations in non-collagenous OI genes. Further analysis of OI patients negative for collagen mutations, is required.
authors: Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen, Hue city, 530000, Vietnam. binhthuybi@yahoo.com.|Department of Traumatology and Orthopaedics, University of Tartu, Puusepa 8, 51014, Tartu, Estonia. binhthuybi@yahoo.com.|Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia. binhthuybi@yahoo.com.
authors: Binh
authors: B
authors: Ho Duy
authors: Department of Traumatology and Orthopaedics, University of Tartu, Puusepa 8, 51014, Tartu, Estonia.
authors: Lidiia
authors: L
authors: Zhytnik
authors: Department of Traumatology and Orthopaedics, University of Tartu, Puusepa 8, 51014, Tartu, Estonia.|Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia.
authors: Katre
authors: K
authors: Maasalu
authors: Department of Pathophysiology, University of Tartu, Ravila 19, Tartu, 50411, Estonia.
authors: Ivo
authors: I
authors: Kändla
authors: Department of Pathophysiology, University of Tartu, Ravila 19, Tartu, 50411, Estonia.
authors: Ele
authors: E
authors: Prans
authors: Department of Pathophysiology, University of Tartu, Ravila 19, Tartu, 50411, Estonia.
authors: Ene
authors: E
authors: Reimann
authors: Department of Traumatology and Orthopaedics, University of Tartu, Puusepa 8, 51014, Tartu, Estonia.|Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia.
authors: Aare
authors: A
authors: Märtson
authors: Centre of Translational Medicine, University of Tartu, Ravila 14a, Tartu, 50411, Estonia.|Department of Pathophysiology, University of Tartu, Ravila 19, Tartu, 50411, Estonia.
authors: Sulev
authors: S
authors: Kõks
mesh_terms: D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D014744:Vietnam
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain
keywords: Bone fragility; Collagen type I; Osteogenesis imperfecta; Sanger sequencing