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Case Reports
. 2025 May;197(5):e63972.
doi: 10.1002/ajmg.a.63972. Epub 2024 Dec 22.

A Deep Intronic Splice Variant in COL1A1 Causing Osteogenesis Imperfecta Type II

Mackenna E Schouw  1   2 , Claudia A L Ruivenkamp  1 , Tamara T Koopmann  1 , Gijs W E Santen  1 , Peter G J Nikkels  3 , Karin van der Tuin  1   4
Affiliations
Case Reports

A Deep Intronic Splice Variant in COL1A1 Causing Osteogenesis Imperfecta Type II

Mackenna E Schouw et al. Am J Med Genet A. 2025 May.

Abstract

Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.2451 + 77C > T in intron 35 of COL1A1, which resulted in aberrant splicing and the in-frame addition of 75 nucleotides into the mRNA. These patients highlight the importance of considering deep intronic variants in type 1 collagen genes in patients with high suspicion of OI, which may be missed with conventional genetic analysis.

Keywords: COL1A1; case report; deep intronic splicing variants; lethal osteogenesis imperfecta.

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References

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