Document Detail


Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation.
MedLine Citation:
PMID:  20569259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.
Authors:
S K Hashmi; C Allen; R Klaassen; C V Fernandez; R Yanofsky; E Shereck; J Champagne; M Silva; J H Lipton; J Brossard; Y Samson; S Abish; M Steele; K Ali; N Dower; U Athale; L Jardine; J P Hand; J Beyene; Y Dror
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical genetics     Volume:  79     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-07     Completed Date:  2011-08-02     Revised Date:  2011-12-06    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  448-58     Citation Subset:  IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Marrow Failure and Myelodysplasia Program, Division of Haematology/ Oncology and Cell Biology Program, Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Bone Marrow Diseases* / diagnosis,  genetics
Exocrine Pancreatic Insufficiency* / diagnosis,  genetics
Female
Genetic Association Studies
Hemoglobinuria, Paroxysmal* / diagnosis,  genetics
Humans
Lipomatosis*
Male
Mutation

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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