A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.
OBJECTIVE
Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease.


METHODS
Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes.


RESULTS
Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined.


CONCLUSIONS
A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.
Tamary
H
H
Pediatric Hematology-Oncology Center and Imaging Department, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel. htamary@post.tau.ac.il
Yaniv
I
I
Stein
J
J
Dgany
O
O
Shalev
Z
Z
Shechter
T
T
Resnitzky
P
P
Shaft
D
D
Zoldan
M
M
Kornreich
L
L
Levy
R
R
Cohen
A
A
Moser
R A
RA
Kapelushnik
J
J
Shalev
H
H
D000740:Anemia / Q000235:genetics* / Q000628:therapy; D018912:Arabs; D001792:Blood Platelets / Q000648:ultrastructure; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000473:pathology; D004920:Erythropoiesis; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007223:Infant; D008854:Microscopy, Electron; D009503:Neutropenia / Q000235:genetics* / Q000628:therapy; D009504:Neutrophils / Q000473:pathology; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics* / Q000628:therapy; D034061:Thrombopoiesis / Q000235:genetics*