TY - JOUR
T1 - Explanation for mild and severe osteogenesis imperfecta phenotypes due to splice variants at c.2029-1 in COL1A1
AU - Radhakrishnan, Periyasamy
AU - Somashekar, Puneeth H.
AU - Girisha, Katta M.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089012258&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089012258&partnerID=8YFLogxK
U2 - 10.1016/j.genrep.2020.100803
DO - 10.1016/j.genrep.2020.100803
M3 - Article
AN - SCOPUS:85089012258
SN - 2452-0144
VL - 21
JO - Gene Reports
JF - Gene Reports
M1 - 100803
ER -