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So far researchers have traced several causes for BWS in altered genes in the 11p15 chromosome region. These altered genes include (according to an article by Dr. DeBaun et.al. published in the American Journal of Human Genetics in 2002): 1. Loss of imprinting (LOI) of LIT1 - approximately in 40-50% of the studied individuals diagnosed with BWS 2. Loss of imprinting (LOI) of IGF2 - approximately in 10-15% of the studied individuals diagnosed with BWS 3. Abnormal methylation of H19 - approximately in 15% of the studied individuals diagnosed with BWS 4. UniParental Disomy (UPD) of 11p15 - approximately in 10% of the studied individuals diagnosed with BWS 5. Interruptions in KvLQT1 gene - rare (less than 5% of the studied individuals diagnosed with BWS) 6. Mutations of the p57KIP2 gene - rare (less than 5% of the studied individuals diagnosed with BWS) Genetic tests available on the market differ in respect to how many of these genes are actually tested. Some genetic tests only cover a subset of the above list - and hence provide only a partial answer - that is, a positive answer on the test would indeed confirm that the individual tested has BWS, while a negative answer on the test only means that the individual does not have any alterations in the genes tested, but very well may have alterations in the genes not tested. Also, as research of BWS is still ongoing, it is possible that BWS may be caused by an alteration in a gene which is not in the above list (that is has not been identified yet by researchers). This is why the recommendation is to stick to the clinical diagnosis of BWS (i.e. to follow the screening protocol), regardless of any genetic testing result. Genetic tests also differ on whether they give back answers to the parents, how long it takes to receive an answer and the incurred costs. Some tests are defined for research purposes, and it depends on the researcher and on the various regulations imposed on him/her whether he can or is willing to provide the answer back to parents. Even if you do get an answer back from a research test it usually takes many months and sometimes over a year, and usually the test is free. Commercial labs provide the tests for a fee, but of course they always give back answers and they usually do so quite promptly (a month or so). Also some institutes require that you visit there in person, while others can accept blood samples to be sent to them by courier. If you test the child and his/her parents, and you find that the child has an alteration in a given gene, and one of the parents has the same exact alteration, you can deduce with high certainty that the altered gene was passed on to the child from one of the parents (familial BWS), and hence the likelihood of the same couple having another child with BWS is relatively high (most researchers estimate this at about 50%), while if the altered gene of the child does not appear with either parents, you can deduce with high certainty that the BWS of the child was a sporadic mutation, and the likelihood of that same couple having another child with BWS is very small. Some researchers argue that recognizing familial BWS requires finesse and a close analysis of the family history and family photos. Below find a list of labs which provide genetic tests for BWS which we rounded up from the experience of various parents in our group, which should provide you with a good starting point. The relevant information (price, list of genes tested, etc.) is subject to change over time, so it's recommended to check with each lab for current information. Best of luck, Yaki 1. We did the test in Toronto Sick Children's hospital in 2000, within a research study (no fee was required from us). The samples were accepted by courier. The tests done there at the time only covered UPD in Chromosome 11p15 and mutations in p57KIP2 gene. It took a long time to get the results back (over a year, and when we finally "nagged" the lab directly we received answers...). If you are interested in this option I recommend you get in touch with Ms. Cheryl Shuman, who has been most helpful. Her contact info is: Cheryl Shuman, MS, CGC Director, Genetic CounsellingAsst. Professor Division Clinical & Metabolic Genetics Molecular Genetics & Microbiology The Hospital for Sick Children Program Director 555 University Avenue M.Sc. Program in Genetic Counselling Toronto, Ontario, CAN University of Toronto M5G 1X8 fax: 416-813-5345 phone: 416-813-7550 Email: cshuman@sickkids.ca 2. Dr. DeBaun runs a very comprehensive test for BWS in Washington University in St. Louis as part of the BWS registry. However, I'm not sure if he is currently willing to accept blood samples by courier or if he is currently giving back answers to parents nor if there is a fee for the test. Many parents in our group did this test in 2001, when it was free of charge but required a visit to St. Louis (which many of these parents visited anyway during the 2001 BWS conference) and it took over a year to receive the answers. Dr. DeBaun's email is debaun_m@pcfnotes1.wustl.edu and his other contact info is on our website www.geocities.com/beckwith_wiedemann/drsresearchers.html see also http://www.surgery.wustl.edu/bjcmdl/BWS.htm for more information on this testing and the BWS Registry (contact Cindy Terrill to add your information to the BWS Registry). 3. A USA based commercial lab named CompGene runs a test for BWS at a charge of approximately $473. They accept blood samples by courier and provide an answer within 10 working days. Their contact info is: 4. Our geneticist read in an article published by Dr. Mannens in Human Molecular Genetics of 2001, about a test run in Holland which seemed to be quite comprehensive. Dr. Mannens is willing to accept out of country samples by courier, and the fee for the test is approximately 1,200 Dutch Floren (approximately $500 US). The contact info:
Dr. M,M.A.M. Mannens 5. Oksana did the genetic test for BWS for her family in Moscow in 2002. It takes 2-3 weeks to get an answer and they accept blood samples delivered by courier. In 2002 they tested for UPD, LOI of IGF2, and LOI of LIT1. They did not yet test the P57KIP2 and H19. They were going to start testing for P57KIP2 "soon" (perhaps they already started) and at that time had no definite plans yet for testing H19. The cost is around $60. They are not a commercial lab - they are genetic research lab of the Russian Academy of Science (most of the people there are well known PhDs in genetics). For more information please contact Oksana at rom@uonline.ru
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this page last modified: 06/04/2007
