Complete COL1A1 allele deletions in osteogenesis imperfecta

Purpose: To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. Methods: The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. Results: In four families with mild osteogenesis imperfecta and no other phenotypic abnormalities, a deletion of the complete COL1A1 gene on one allele was detected, a molecular finding that to our knowledge has not been described before, apart from a larger chromosomal deletion detected by fluorescent in situ hybridization encompassing the COL1A1 gene in a patient with mild osteogenesis imperfecta and other phenotypic abnormalities. Microarray analysis in three of the four families showed that it did not concern a founder mutation. Conclusion: The clinical picture of complete COL1A1 allele deletions is a comparatively mild type of osteogenesis imperfecta. As such, multiplex ligation-dependent probe amplification analysis of the COL1A1 gene is a useful additional approach to defining the mutation in cases of suspected osteogenesis imperfecta type I with no detectable mutation. Genet Med 2010:12(11):736-741