Shwachman diamond support uk - Medical Information.

Great Ormond Street Hospital

Great Ormond Street Hospital is a specialist children's hospital that has been caring for children with Shwachman-Diamond syndrome for many years. This new clinic commenced on October 2003 at the request of the Shwachman-Diamond syndrome society. It is a multi-disciplinary clinic that will see children until the age of 18 years. The clinic is held on three times a year, (February, June and October) on the second Tuesday of the month. The clinic works in very close liaison with local paediatricians to support the children's care and will only accept new referrals with your paediatrician's agreement. New referrals should be sent to Dr Shah. Patient accommodation given sufficient notice can be available for those who travel long distances

The clinic offers a multi-disciplined approach to Shwachman-Diamond syndrome. The aim is to offer specialist medical care, support and knowledge for children with Shwachman-Diamond syndrome. The consultants have active research interests in this field and you and your children may be asked to help in future research studies.

The team includes;
Lead Consultants / Permanent clinic members
Dr Neil Shah (Consultant Paediatric Gastroenterologist)
Dr Phillip Ancliff (Consultant Paediatric Haematologist)
Dr Carol Mason (Consultant Paediatric Dentist)
Gastroenetrology Specialist senior dietician

Supporting Medical staff
Dr Mandy Byron (Psychologist)
Dr Martin Schwarz (Manchester)
Orthopaedic Consultants at Great Ormond Street
Great Ormond Street Feeding Clinic

The Genetic Defect in Shwachman Diamond Bodian Syndrome

The SDS gene - called SBDS ( the B is to recognize Dr Martin Bodian, who was an eminent pathologist based at Great Ormond St. Hospital, London) - was identified in late 2002. The scientific paper was published in the journal "Nature Genetics", with the full reference given below. The recent work follows up on earlier efforts showing that SBDS was in a region of chromosome number 7. The scientists then had to painstakingly test each gene in the region looking for a mutation in the DNA. Each gene contains information encoded in the chemicals that comprise the DNA, these chemicals being called bases. There are four bases in DNA, given the symbols A, T, C & G. An alteration in the sequence of bases may cause a mutation e.g. if an A turns into a G. Often, these changes have no effect because they occur in DNA outside a gene, but if they occur within a gene they can result in a defective message. That's because the DNA makes another molecule called messenger RNA which, in turn, makes the proteins of the cells and body.

The Canadian scientists looked at over one hundred patients with SDS. They found that two mutations were particularly common. This should make screening for these two mutations relatively straightforward. On the other hand, every human has a defective version of the SBDS gene next to the working copy. Such a gene is called a pseudogene, as it does not make a protein and is not required for normal development. It is, in a sense, a relic of evolution. However, the presence of this second gene does complicate genetic analysis, because it makes it difficult for the scientist to be sure they are looking at the real, important gene, or the pseudogene version.

What does the SBDS protein do in the body? Unfortunately, there are few clues from the work done so far. One way scientists try and work out what a gene does is to compare its derived protein sequence with that of proteins of known function. There are some hints from this type of analysis that the SBDS may be involved in working with RNA ( see above, RNA helps in the transfer of genetic information from DNA into protein). Much more work will be required to find out how this or other actions of SBDS cause abnormalities in the pancreas, bone and blood. In the distant future, it may be possible to use gene replacement therapy to treat the SDS and prevent the onset of serious symptoms.

Reference for Original Paper

Mutations in SBDS are associated with Shwachman-Diamond Syndrome.

Nat Genet 2003 Jan;33(1):97-101

Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM.

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University of Cambridge.

Proffesor Alan J Warren.

I was appointed Professor of Haematology at the University of Cambridge in 2003. I have established a specialist clinic at Addenbrooke's NHS Trust for the care of patients with inherited and acquired forms of bone marrow failure, including aplastic anaemia and myelodysplasia.

My research group is situated within the prestigious MRC Laboratory ofMolecular Biology where the primary focus of our current researchprogramme is to elucidate the function of the SBDS gene that is mutated inShwachman-Diamond syndrome (SDS). We initially solved the crystalstructure of an archaeal SBDS protein homologue (Shammas et al., J BiolChem. 2005, 280:19221-9). More recently, using a genetic approach, wediscovered that the yeast SBDS homologue is required for the maturation ofthe large ribosomal subunit (Menne et al. Nat Genet. 2007, 39:486-95). Ourdata link the pathogenesis of SDS to defective ribosome assembly and
suggest novel approaches for the rational design of therapeutics. Ourongoing research combines structural, genetic and biochemical approachesin a variety of model systems to obtain detailed insight into themolecular basis of SDS. We are grateful for generous support from a
Leukaemia Research Specialist Programme, from the Association forInternational Cancer Research and from SDS UK.

More funding is desperatley needed to take forward the work, on the SDS stem cells research.

please send all donations to:

Alan J. Warren
Professor of Haematology, University of Cambridge
Division of Protein & Nucleic Acid Chemistry
MRC Laboratory of Molecular Biology
Hills Road
Cambridge
CB2 0QH

Program in Genetics and Genomic Biology, Room 11-109A, Elm Wing Annex, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8 Canada.