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Shwachman-Diamond Syndrome (SDS) is an autosomal recessive genetic disorder involving multiple organ systems and affecting children and young adults. With the recent identification of the SBDS gene - a novel, highly conserved gene encoding a protein of unknown function - investigations into SBDS function have constituted an active area of scientific research. SBDS has been suggested to function in ribosome biogenesis, adding to the recently growing body of evidence implicating ribosome dysfunction in marrow failure and cancer predisposition.

Shwachman-Diamond Syndrome Gene Questions and Answers
With participation of SDS families from around the world, researchers from the Dr. Johanna Rommens and Dr. Peter Durie laboratories at The Hospital for Sick Children in Toronto have identified the altered gene that causes this disorder in December of 2002.

Does a genetic test for Shwachman-Diamond Syndrome (SDS) exist?

The gene that causes Shwachman-Diamond syndrome has been identified and a number of genetic mutations (mistakes in the gene) have been found in people who have this condition. A genetic test is now available and is available at many testing centers. Please refer to the Gene Testing section on this web site.

(Additional information from the SDS Registry, which is not part of this original Q&A, states that "Genetic testing of siblings in families of patients with Shwachman-Diamond syndrome is important and necessary. A recent study through the North-American Shwachman-Diamond Syndrome Registry looking at initial symptoms at the time of diagnosis reports that as many as half of patients with SDS may first see a doctor without the classic symptoms of neutropenia, diarrhea or poor growth/failure to thrive. These results included some siblings of patients with Shwachman-Diamond syndrome who were otherwise without symptoms, and who were diagnosed with the SDS upon genetic testing. All siblings of patients with SDS is should be tested, as timely diagnosis prior to the development of complications is critical for the best medical management and outcomes, particularly in the case of bone marrow failure, leukemia, or bone marrow transplantation. This is also especially important to ensure that affected siblings are not used as donors for bone marrow transplantation.")

What is the difference between genetic testing in a research lab and a "routine clinical test"?

Research-based genetic testing is different from routine clinical tests. Research procedures are not approved nor standardized, and do not involve the same level of quality control that is required by regulatory authorities for commercial laboratories. The results of research-based tests include a disclaimer stating that the findings do not involve a standardized, approved test, and a caution that there may be errors in the test results.

When will a test be available for my spouse to see if he/she is a carrier?

A genetic test for carrier status is available at the Molecular Genetics Laboratory at The Hospital for Sick Children, Toronto, Canada. Please contact info@shwachman-diamond.org for the current contact information.

Can you test siblings to determine their carrier status?
Current knowledge suggests that people who carry a single SDS mutation do not have clinical symptoms.

Is there more than one gene mutation?

To date, all SDS-associated mutations have been identified in one gene. There are a number of different mutations within this one gene. Two common alterations were found to account for 75% of all mutations in the initial group of families we have tested.

What does identification of the SDS gene mean for the short-term?

In the short term, discovery of the SDS gene will lead to improved diagnosis of the disease since genetic tests are become available. In addition, collected clinical and genetic data can be used to determine if some mutations are associated with distinct SDS features.

What is next for research?

The focus of research will now shift towards studying the gene that is altered in SDS. We need to learn more about this gene, its role in cells and tissues, how it works, and what goes wrong in SDS.This insight will be crucial to learn how mistakes in this gene lead to the clinical symptoms of SDS, including blood, bone and digestive problems. Ultimately, this may lead to development of new therapies for SDS. It is now widely accepted that SDS falls in the category of a ribosomal disease meaning that the ribosome is affected.

Will finding the gene mean that there is a "cure" (gene therapy)?

Intense research efforts worldwide are focused at correcting genetic defects by gene therapy. However, there are numerous obstacles and safety concerns about introducing a corrected gene into human cells. We hope that breakthroughs in this field will make this an option for SDS patients in the future.

Why must I go through my physician to receive this genetic information?

Issues arising from genetic test results can be very complex. Your physician can help explain the results and prepare you for the possible implications of having this information. Your doctor may also decide to refer you to a genetic counselor for additional consultation.

Is genetic counseling important?

The purpose of genetic counseling is to answer questions you may have and also to prepare you to deal with the results of genetic testing. It is important that you fully consider the risks and benefits related to genetic testing. It may not provide you with clear and final answers regarding the health of your child or other family members and the results can be inconclusive. There are other potential risks of learning about gene alternations in your family that cannot be predicted. There may be unknown personal, legal and social consequences, and there may be implications for obtaining life and medical insurance.

When will my doctor receive the results?

Genetics research is complex and time-consuming. There may not have any findings for a small percentage of patients. In some cases, this will be due to inadequate amounts of DNA. In these cases, you will be requested to send an additional blood sample in order to complete genetic testing. Families who fit into this category will be contacted to discuss further testing.

Will I need to have my research results confirmed in a registered diagnostic facility?

Yes. This is particularly important if the genetic test results are to be used for genetic counseling, or if the clinical diagnosis is in doubt. This should be discussed with your doctor or a genetic counselor.

If mutations are not identified, does this mean I don't have SDS?

A diagnosis of SDS cannot be ruled out based on lack of genetic evidence. This is because some types of genetic mutations are rare and/or very difficult to detect. Genetic testing does not replace the need for careful investigation and monitoring of clinical symptoms, including pancreatic function and hematological problems. The published consensus statement provides the clinical criteria for diagnosis of SDS (Rothbaum et al., 2002. Shwachman-Diamond syndrome: Report from the international conference. Journal of Pediatrics. vol 141, p266-270). A new consensus has been published in 2011. Please click here to view it.

Thanks to these dedicated doctors and Fellows below who wrote and answered these important questions above.

Graeme R.B. Boocock
Lynda Ellis, R.N.
Nicole Richards
Jodi Morrison

Check below for more information.

NIH Genetics Home Reference on Shwachman-Diamond Syndrome

This web site http://www.kumc.edu/gec/prof/cytogene.html is a compilation of links to images, educational resources, lectures, and support groups all focused on cytogenetics. Although not for those new to deciphering medical results, those that are ready for more detailed information should find it very useful.