Classical osteogenesis imperfecta (OI), or brittle bone disease , is a well described autosomal dominant bone dysplasia caused by mutations in the genes encoding type I collagen, the major protein of bone matrix. However, genetic testing has shown that 10-15% of clinical OI is not caused by collagen defects. Furthermore, recessive forms of OI have been postulated since 1979. We have recently identified two genes which cause recessive osteogenesis imperfecta (OI), a lethal or severe heritable bone disorder. Null mutations of genes encoding the components of the prolyl 3-hydroxylation complex, a complex in the endoplasmic reticulum which is responsible for a specific post-translational modification of collagen, result in severe/lethal OI. These findings have resulted in a new paradigm of collagen-related bone disorders. In addition, we are now able to provide accurate genetic information to individuals who have OI in the absence of collagen structural defects. In one gene, we identified a recurring mutation in 6 children of West African or African-American descent. We have also identified 5 additional carriers by testing a small collection of anonymous African-American newborn blood samples. We would like to expand our screening efforts for this recurring mutation and test 1500 coded newborn heel spots from the state of Maryland, as well as 1500 leukocyte genomic DNA samples from Washington D.C., in order to generate a more precise estimate of the carrier rate of this mutation in the African-American population. In addition, we plan to test up to 3900 leukocyte genomic DNA samples from Nigeria and Ghana, in order to determine the region of origin and prevalence of the recurring mutation.
Estimated Enrollment: |
0 |
Study Start Date: |
January 2008 |
Classical osteogenesis imperfecta (OI), or brittle bone disease , is a well described autosomal dominant bone dysplasia caused by mutations in the genes encoding type I collagen, the major protein of bone matrix. However, genetic testing has shown that 10-15% of clinical OI is not caused by collagen defects. Furthermore, recessive forms of OI have been postulated since 1979. We have recently identified two genes which cause recessive osteogenesis imperfecta (OI), a lethal or severe heritable bone disorder. Null mutations of genes encoding the components of the prolyl 3-hydroxylation complex, a complex in the endoplasmic reticulum which is responsible for a specific post-translational modification of collagen, result in severe/lethal OI. These findings have resulted in a new paradigm of collagen-related bone disorders. In addition, we are now able to provide accurate genetic information to individuals who have OI in the absence of collagen structural defects. In one gene, we identified a recurring mutation in 6 children of West African or African-American descent. We have also identified 5 additional carriers by testing a small collection of anonymous African-American newborn blood samples. We would like to expand our screening efforts for this recurring mutation and test 1500 coded newborn heel spots from the state of Maryland, as well as 1500 leukocyte genomic DNA samples from Washington D.C., in order to generate a more precise estimate of the carrier rate of this mutation in the African-American population. In addition, we plan to test up to 3900 leukocyte genomic DNA samples from Nigeria and Ghana, in order to determine the region of origin and prevalence of the recurring mutation.