Abstract:

bjective To summarize the clinical features and gene mutation characteristics of a de novo COL1A2 gene mutation in a fetus with severe osteogenesis imperfect (OI), and to provide evidence for prenatal counseling.Methods DNA was extracted from the fetal abortion tissues, and primers of the whole exons and splicing sites of COL1A1 and COL1A2 genes were designed. Using Sanger sequencing, the fetal sequences of the whole exons and splicing sites of COL1A1 and COL1A2 genes were analyzed and confirmed with the parents' samples. According to HGMD, literatures on clinical symptoms of the diseases caused by COL1A2 mutation were reviewed.Results The variants on both COL1A1 and COL1A2 gene were detected. On COL1A2 gene a de novo heterozygous mutation (c.3142G>T, p. Glu1048Cys) was detected, which had never been reported in dbSNP, HGMD and osteogenesis imperfecta & Ehlers-Danlos syndrome variant databases. Compared with the common database and online prediction software the mutation was predicted to be a the disease-causing mutation. HGMD professional version was searched with "COL1A2"and 387 disease-causing mutations were found to be related to 21 diseases or their subtypes. Ninety-two percent of the mutations caused OI or its subtypes; others caused Ehlers-Danlos syndrome or its subtype. Combined with the clinical symptoms of the disease caused by COL1A2 gene, the fetus was more consistent with the OI type Ⅱ. Conclusion A fetus OI type Ⅱ caused by a de novo mutation in COL1A2（c.3142G>T, p. Glu1048Cys）was diagnosed with prenatal ultrasound imaging and genotyping. Glycine in 400 to 480 amino acid and MLBR 3 region of the protein encoded by COL1A2 gene replaced by aspartate acid or glutamic will cause sever OI. This article provides the basis for accurate prediction of fetal outcome and clinical decision-making.