|
|
Blood, 1 July 2005, Vol. 106, No. 1, pp. 356-361.
Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2004-11-4371.
 Previous Article | Next Article 
Submitted November 16, 2004
Accepted January 14, 2005
Hematological abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship
Taco W Kuijpers*, Mariel Alders, Anton T Tool, Clemens Mellink, Dirk Roos, and Raoul C Hennekam
Emma Children's Hospital, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands; Sanquin Research at CLB, and Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands
Dept. of Clinical Genetics, Institute for Human Genetics, Academic Medical Center (AMC), Amsterdam, The Netherlands
Sanquin Research at CLB, and Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands
Emma Children's Hospital, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands; Dept. of Clinical Genetics, Institute for Human Genetics, Academic Medical Center (AMC), Amsterdam, The Netherlands
* Corresponding author; email: t.w.kuijpers{at}amc.uva.nl.
Shwachman-Diamond syndrome (SDS) is an autosomal-recessive disorder characterized by short stature, exocrine pancreatic insufficiency, and hematological defects. The causative SBDS gene was sequenced in 20 of 23 unrelated patients with clinical SDS. Mutations in the SBDS gene were found in 75%, being identical in 11 patients. Hematological parameters for all three lineages were determined over time such as absolute neutrophil counts (ANC), granulocyte functions, and erythroid and myeloid colony formation (BFU-E and CFU-GM) from hematopoietic progenitor cells, HbF%, and platelet counts.
Persistent neutropenia was present in 43% in the absence of apoptosis and unrelated to chemotaxis defects (in 65%) or infection rate. Irrespective the ANC in vivo, abnormal CFU-GM was observed in all SDS patients tested (14 of 14), whereas BFU-E was less often affected (9 of 14). Cytogenetic aberrations occurred in 5 of 19 patients in the absence of myelodysplasia. One child died during allogeneic bone marrow transplantation.
In conclusion, neutropenia and defective chemotaxis did not result in severe clinical infection in SDS. CFU-GMs were impaired in all patients tested. From the SBDS sequence data, we conclude that in genetically proven SDS patients a genotype-phenotype relationship in SDS does not exist in clinical and hematological terms.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Orelio and T. W. Kuijpers
Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics
Haematologica,
March 1, 2009;
94(3):
409 - 413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Drewniak, J.-J. Boelens, H. Vrielink, A. T.J. Tool, M. C.A. Bruin, M. van den Heuvel-Eibrink, L. Ball, M. D. van de Wetering, D. Roos, and T. W. Kuijpers
Granulocyte concentrates: prolonged functional capacity during storage in the presence of phenotypic changes
Haematologica,
July 1, 2008;
93(7):
1058 - 1067.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Brown and R Buchdahl
Shwachman-Diamond syndrome in a child presenting with cystic fibrosis-type symptoms and a false-positive sweat test
J R Soc Med,
July 1, 2008;
101(Supplement_1):
39 - 42.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Rawls, A. D. Gregory, J. R. Woloszynek, F. Liu, and D. C. Link
Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential
Blood,
October 1, 2007;
110(7):
2414 - 2422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. W. Kuijpers, R. v. Bruggen, N. Kamerbeek, A. T. J. Tool, G. Hicsonmez, A. Gurgey, A. Karow, A. J. Verhoeven, K. Seeger, O. Sanal, et al.
Natural history and early diagnosis of LAD-1/variant syndrome
Blood,
April 15, 2007;
109(8):
3529 - 3537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Nishimura, E. Nakashima, Y. Hirose, T. Cole, P. Cox, D. H Cohn, D. L Rimoin, R. S Lachman, Y. Miyamoto, B. Kerr, et al.
The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type
J. Med. Genet.,
April 1, 2007;
44(4):
e73 - e73.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Wessels, T. Srikantha, S. Yi, S. Kuhl, L. Aravind, and D. R. Soll
The Shwachman-Bodian-Diamond syndrome gene encodes an RNA-binding protein that localizes to the pseudopod of Dictyostelium amoebae during chemotaxis
J. Cell Sci.,
January 15, 2006;
119(2):
370 - 379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Marsh
Making Therapeutic Decisions in Adults with Aplastic Anemia
Hematology,
January 1, 2006;
2006(1):
78 - 85.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Guinan
Aplastic Anemia: Management of Pediatric Patients
Hematology,
January 1, 2005;
2005(1):
104 - 109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
