Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta

Abstract

BackgroundThe 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.MethodsGenomic 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.ResultsThe 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.ConclusionOur 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.

Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta

“…Quantitative ( n = 47) and structural ( n = 130) variants accounted for 20% and 57% of defects in collagen I n = 230, respectively. As reported in previous studies (Ho Duy et al, ; Lindahl et al, ; Zhytnik et al, ), the relationship between the mutation type and the severity of phenotype was complex: in those patients with defects in type I collagen, structural variants were responsible for 39% of probands of Type I (46/119), whereas there were also six patients of Type IV and one of Type III who had quantitative defects (4%, 7/161).…”

De novo and inherited pathogenic variants in collagen‐related osteogenesis imperfecta

“…COL1A1/2 mutational analysis was performed with Sanger sequencing. Detailed information has been reported in previous studies (Binh et al, 2017;Ho Duy et al, 2016;Zhytnik et al, 2017). In this current study, the cohort was comprised of Estonian (27), Vietnamese (57), and Ukrainian (62) OI patients and represented the youngest affected proband of every kindred.…”

The pathogenicity of novel GUCY2D mutations in Leber congenital amaurosis 1 assessed by HPLC-MS/MS

“…All amplifications were examined by electrophoresis using 2% agarose gels and sequenced by BioSune Biotechnology Co., Ltd. (Shanghai, China). The sequencing results were further compared and analyzed by Mutation Surveyor [8].…”