Samples from forty-five patients and family members from the Old Order Amish with osteogenesis imperfecta were collected in a study by Dr. Daniel McBride of the University of Maryland. Osteogenesis imperfecta (OI) (OMIM 166200) is a heritable disease with a heterogeneous clinical presentation typically classified into four severity types. Disease severity ranges from a mild form with blue sclerae, little or no bone deformity, and few fractures to a perinatal lethal form with marked bone deformity, compressed femurs, and mineralization defects. Currently, there is increased recognition that the same type of type I procollagen mutation in related and unrelated individuals can exhibit phenotypic variation.
The samples were collected from four families and of the forty-five, seventeen are unaffected and twenty-eight are affected. There are twenty-five females and twenty males with an age range from 7 to 87 years. A single mutation, 2237G>T, in exon 35 of the collagen IA2 gene (OMIM 120160), results in a Gly610Cys change in the protein. This form of osteogenesis imperfecta is inherited in an autosomal dominant manner. All family members with the mutation can be traced to a single founding couple approximately 150 years ago.
The clinical parameters collected for the study and available for the catalog include height, weight, age, fracture history, and detailed bone density measurements (DEXA). An Excel spreadsheet is available for download density measurements (DEXA) .
Since the clinical presentation varies greatly, this population of samples should be useful for identification of modifier genes. See "Variable expressivity of a COL1A2 gly-610-cys mutation in a large Amish pedigree." McBride, D.J., Streeten, E.A., Mitchell, B.D., Shuldiner, A.R. Am. J. Hum. Genet. 71, Supplement. Abstract 1047 (2002).
The relationship of these individuals is shown in the following sibship pedigrees: