Atypical osteogenesis imperfecta caused by a 17q21.33 deletion involving COL1A1.

The majority of patients with osteogenesis imperfecta (OI) have a mutation in COL1A1 or COL1A2. Whole gene deletions appear to be an infrequent cause of OI. Here we describe a 8-year-old female with OI, intellectual disability and behavioural problems caused by a 2.3Mb deletion of chromosome 17q21.33 containing COL1A1. This deletion was detected using array comparative genomic hybridization (aCGH), performed to identify a cause for her intellectual disability. DLX3, DLX4, CA10, CACNA1G, ITGA3 and XYLT2 were also deleted and likely to be contributing to her phenotype. This case provides further evidence that aCGH is an important test for children with OI when it is associated with additional features, such as intellectual or behavioural disability. With greater use of aCGH, the proportion of patients with atypical OI due to contiguous gene deletions or copy number variation elsewhere in the genome is likely to become clearer. This case also provides evidence that deletions in COL1A1 resulting in haploinsuffiency are pathogenic and that a contiguous gene deletion may modify the patient’s phenotype.