- Brittle bone disease
- Fragilitas ossium
- Vrolik disease
Your QuestionI have a cousin with osteogenesis imperfecta. Neither of his parents has the dominant gene. Is there a genetic test that can be done to determine whether I am a carrier?
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Most types of osteogenesis imperfecta (OI) have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. The altered copy of the gene may be inherited from an affected parent, or it may occur for the first time in an affected individual. Each child of an individual with a dominantly inherited form of OI has a 50% (1 in 2) chance of inheriting the . The child would have the same OI-causing mutation as the parent, although the child’s symptoms may be milder or more severe than the parent’s symptoms. Many people with type I or type IV OI inherit a mutation from a parent who has the disorder, while most infants with more severe forms (such as type II and type III) have no history of the condition in their family and have a new (sporadic) mutation that occurred for the first time in their cells.
Less commonly, osteogenesis imperfecta has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means that two copies of the gene in each cell are altered. The parents of a child with an autosomal recessive disorder typically are not affected, but each carry one copy of the altered gene (they are referred to as carriers). When two carriers for an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier, and a 25% chance to not have the condition and not be a carrier. The children of an individual with an autosomal recessive type of OI are always carriers for a . Some cases of osteogenesis imperfecta type III are autosomal recessive, as well as some other types of OI that are caused by mutations in the CRTAP or LEPRE1 genes.
It is recommended that couples at risk of having a child with OI seek genetic counseling before conception, or as early in the pregnancy as possible. A genetic counselor can provide information on OI genetics and prenatal diagnosis. Instructions for locating a genetics professional are provided in the Services tab of the home page for this topic.
When the parents of an affected individual do not have any signs or symptoms of OI, there is still a risk of about 5% for siblings of the affected individual to have OI. This is because it is possible (but uncommon) for one of the parents to have somatic and/or germline mosaicism. Somatic cells are all of the cells of the body except the egg and sperm cells. Somatic mosaicism means that there are two or more genetic cell lines within the cells of the body (i.e. one cell line with the disease-causing mutation and one cell line without). Germline cells are the reproductive cells (egg and sperm cells). Germline mosaicism means that there are two or more genetic cell lines that are present only in the egg or sperm cells. A fact sheet with additional information about mosaicism is available on the Centre for Genetics Education's Web site and can be viewed by clicking here.
Prenatal testing for at-risk pregnancies can be performed by analysis of collagen made by fetal cells obtained by chorionic villus sampling (CVS) at about ten to 12 weeks' gestation if an abnormality of collagen has been identified in cells from the affected individual. Analysis of collagen after an amniocentesis (usually performed at 15-20 weeks gestation) is not useful, because the cells obtained do not produce type I collagen. However, prenatal testing can be performed by analyzing the genes (molecular genetic testing) if the specific mutation has been identified in the affected relative.
GeneTests lists the names of laboratories that are performing genetic testing for different types of osteogenesis imperfecta. To view the contact information for the clinical laboratories conducting testing, click here and click on "Testing" next to the type of OI in which you are interested. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or genetics professional. Genetics professionals, such as genetic counselors, can also explain the inheritance of OI in detail including information about genetic risks to specific family members.
The following online resources can help you find a genetics professional in your community:
- The National Society of Genetic Counselors provides a searchable directory of US and international genetic counseling services.
- The American College of Medical Genetics has a searchable database of US genetics clinics.
- The University of Kansas Medical Center provides a list of US and international genetic centers, clinics, and departments.
- The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.
- Steiner RD, Pepin MG, Byers PH. Osteogenesis Imperfecta. GeneReviews. 2005; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=oi. Accessed 4/29/2009.
- Krakow D. OI Issues: Pregnancy Considerations for women with OI. Osteogenesis Imperfecta Foundation. 2007; http://www.oif.org/site/PageServer?pagename=PregOI. Accessed 4/29/2009.
- Osteogenesis imperfecta. Genetics Home Reference (GHR). 2007; http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta. Accessed 11/11/2011.
- Robert D Steiner, Melanie G Pepin, Peter H Byers. Osteogenesis Imperfecta. GeneReviews. January 28, 2005; http://www.ncbi.nlm.nih.gov/books/NBK1295/. Accessed 10/5/2011.