A novel cryptic splice site mutation in COL1A2 as a cause of osteogenesis imperfecta.

ABSTRACT: Osteogenesis imperfecta (OI) is an inherited genetic disorder characterized by frequent bone fractures and reduced bone mass. Most cases of OI are caused by dominantly inherited heterozygous mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2. Here we describe a five-year-old boy with typical clinical, radiological and bone ultrastructural features of OI type I. Establishing the molecular genetic cause of his condition proved difficult since clinical exome and whole exome analysis was repeatedly reported negative. Finally, manual analysis of exome data revealed a silent COL1A2 variant c.3597 T > A (NM_000089.4), which we demonstrate activates a cryptic splice site. The newly generated splice acceptor in exon 50 is much more accessible than the

SUBMITTER: El-Gazzar A 

PROVIDER: S-EPMC8339231 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature