Abstract
BackgroundOsteogenesis imperfecta (OI) is a collagen-related bone dysplasia leading to a susceptibility to fractures. OI can be caused by mutations in several genes including BMP1. It encodes two isoforms, bone morphogenetic protein 1 (BMP1) and mammalian tolloid (mTLD); both have proteolytic activity to remove the C-propeptide from procollagen.Case presentationWe report a Thai OI patient who had his first fracture at the age of three months. Using next generation sequencing, we successfully identified two novel compound heterozygous BMP1 mutations. One mutation, c.796_797delTT (p.Phe266Argfs*25) affects both BMP1 and mTLD isoforms, while the other, c.2108-2A > G, affects only the BMP1 isoform. Preservation of the mTLD may explain the relatively less severe clinical phenotype in this patient. Intravenous bisphosphonate was given from the age of 8 months to 5 years. He was free from fractures for 9 months before discontinuation.ConclusionThis case expands the mutation spectrum of BMP1, strengthens the correlation between genotype and phenotype, and supports the benefits of bisphosphonate in OI patients with BMP1 mutations.
Highlights
Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia leading to a susceptibility to fractures
Osteogenesis imperfecta (OI), a brittle bone disease, is a collagen-related bone dysplasia characterized by bone fragility leading to a susceptibility to fractures
More than 90% of OI patients are caused by mutations in COL1A1 (Collagen Type I Alpha Chain) and COL1A2 (Collagen Type II Alpha Chain), inherited in an autosomal dominant manner
Summary
We described an OI patient with two novel compound heterozygous mutations in BMP1. One of the two is expected to preserve the mTLD isoform, which may lead to his relatively mild phenotype.
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