We report a fetus aborted at 18 weeks of gestation with lethal osteogenesis imperfecta (OI) carrying a de novo a canonical splice site variant c.2029G > T in COL1A1 (NM_000088.3) identified by exome sequencing. The cDNA change at 2029th position (c.2029G > A and c.2029G > C) of COL1A1 was already reported to cause milder forms of OI. We demonstrate the functional consequences of two single nucleotide transitions, i.e. Guanine to Thymine (G > T) and Guanine to Adenine (G > A) of COL1A1ng. We show the milder OI phenotype caused by the variant c.2029-1G > A is due to haploinsufficiency and severe form of OI caused by the variant, c.2029-1G > T is due to the dominant negative effect on COL1A1 protein.
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