A 5 years 3 months old boy born of a third degree consanguineous union sustained multiple fragility fractures involving the forearm and legs since age 3 years. Deformities of the lower limbs due to repeated fractures were present. He had normal hearing, development and dentition and no family history of repeated fractures, deformities, hearing or dental problems. On examination dentition was normal, sclerae white, no birth marks, pallor or organomegaly.
Bone turnover, Vitamin D, PTH, coeliac screen urine Calcium/creatinine, pH and electrolytes were all normal. Skeletal survey demonstrated normal bone density,Z score : AP spine: z+0.1 Total body: +0.7. Long bone fracture sites demonstrated poor callus formation, normal vertebrae, no bone dysplasia.
Clinical exome revealed a homozygous missense pathogenic mutation in Exon 1 of the Bone Morphogenetic Protein 1 c.34G>V (p.Gly12Arg) causing Osteogenesis Imperfecta type 13.The BMP1 gene on chromosome 8p21.3 is a multifunctional protein acting as a procollagen type 1 C-terminal propeptide endopeptidase. Inactivation of BMP1 impairs proteolytic removal of the carboxyl terminal propeptide from procollagen type 1 and the normal assembly of mature collagen type 1 fibrils
Autosomal recessive mutations result in clinical type 3 (moderate to severe) and genetic type 13 OI.