Explanation for mild and severe osteogenesis imperfecta phenotypes due to splice variants at c.2029-1 in COL1A1

Radhakrishnan, Periyasamy and Somashekar, Puneeth H and Katta, Girisha M (2020) Explanation for mild and severe osteogenesis imperfecta phenotypes due to splice variants at c.2029-1 in COL1A1. Gene Reports, 21. pp. 1-5. ISSN 2452-0144

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: COL1A; osteogenesis imperfecta; letha; dominant negative effect; haploinsufficiency; minigene assay.
Subjects: Medicine > KMC Manipal > Paediatrics
Depositing User: KMC Library
Date Deposited: 08 Jan 2021 05:40
Last Modified: 08 Jan 2021 05:40
URI: http://eprints.manipal.edu/id/eprint/156232

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