Novel mutations in BMP1 induce a rare type of osteogenesis imperfecta

Background: Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. OI patients of autosomal recessive inheritance are extremely rare, of which OI type XIII is attributable to mutation in BMP1 gene. Case report: Here, we detect the pathogenic mutations and analyze their relation to the phenotypes in a Chinese family with OI using next-generation sequencing (NGS) and Sanger sequencing. We also evaluate the efficacy of alendronate treatment in the patient with OI type XIII. The clinical phenotypes of the patient included recurrent fractures, muscle weakness, bone deformity, macrocephaly and elbow contractures, but no blue sclera or dentinogenesis imperfecta. High-resolution peripheral quantitative computed tomography revealed high bone mineral density and bone volume, but reduced trabecular numbers, increased porosity and comprised strength in this patient. Novel heterozygous mutations of c.1324G > T (p.Asp442Tyr) and c.148 + 1G > A in BMP1 gene were found in the proband, which would affect the CUB2 domain and the prodomain of mutant proteins. The parents were heterozygous carriers for the two mutations respectively, but with normal phenotype. Conclusions: We report for the first time that the novel pathogenic mutations in BMP1 can lead to the extremely rare OI type XIII, which exhibit unique characters of high bone mass, but with impaired bone microstructure and comprised bone strength. Alendronate is beneficial in increasing bone mineral density and decreasing bone resorption biomarkers, but concerns still remain whether it can reduce fracture incidence in this rare type of OI.