To investigate the clinical characteristics and outcome of fetal and adult period recurrent osteogenesis imperfecta caused by COL1A2 gene mutation in a family.

A pregnant woman with COL1A2 gene variant was selected as the research object in the department of obstetrics in Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University. Clinical data of her fetus and family members were analyzed. Invasive prenatal diagnosis was performed for chromosome G-banding karyotype analysis, chromosome microarray analysis (CMA) and family whole exome sequencing (Trio-WES). Relatives with related phenotypes were accepted Sanger sequencing. Pathogenicity was classified according to the American College of Medical Genetics and Genomics (ACMG) and the update to the interpretation of sequence variation in ClinGen.

The clinical symptom of the fetus was winding bones of the lower limbs. The gravida, the sibling sister and the uncle showed same symptom when they were infants. But the symptom turned to brittle teeth which must be repaired in adult. Trio-WES discovered the gene heterozygous variation in COL1A2 NM_000089.4: c.1127G>T(p.Gly376Val), which was inherited from mother. The inheritance patterns was autosomal dominant inheritance (AD). its pathogenicity was rated as likely pathogenic variation. The siblings and uncles carry the same variation by Sanger sequencing verification. Fetal chromosomal karyotype analysis: 46, XN inv (9) (p12q13). There was no abnormality in CMA.

The gene COL1A2 c. 1127G>T (p. Gly376Val) heterozygous mutation is the etiology of the fetus. The clinical phenotype of this locus variation in COL1A2 gene is time specificity. It was resulting in bone dysplasia without bone fracture in the fetal and neonatal period, and then the phenotype convert into dentinogenesis imperfecta as childhood.