Long-term outcome of hemizygous and heterozygous carriers of a germline GATA1G208R mutation
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ulrich Dührsen & Christian P. Kratz & Christian Flotho & Thomas Lauenstein & Martin Bommer & Erika Kِnig & Günter Brittinger & Hermann Heimpel
- چاپ و سال / کشور: 2010
Description
The transcriptional regulator GATA1 is crucially involved in megakaryocytopoiesis and erythropoiesis. Mutations of the gene which is located on the X chromosome have been associated with platelet and red blood cell abnormalities. We identified a family with a GATA1G208R mutation in whom a low male birth rate and frequent miscarriages among heterozygous females suggested increased fetal death in male hemizygotes. Female mutation carriers had normal or near normal hemoglobin levels and platelet counts ranging from normal to severely reduced, probably reflecting skewed X chromosome inactivation. Platelets were dimorphous, and thrombocytopenia was associated with erythroblastosis. The only living male mutation carrier had severe macrothrombocytopenia with life-threatening bleeding episodes, moderate to severe anemia, eosinopenia, skeletal abnormalities, and abundant extramedullary hematopoiesis. Long-term sequelae in the 50-yearold patient included unilateral nephrectomy following misinterpretation of paraspinal hematopoiesis as renal cancer, spinal stenosis which was possibly favored by progressive bone marrow expansion, and severe secondary gout.
Ann Hematol (2011) 90:301–306 DOI 10.1007/s00277-010-1088-9 Received: 12 September 2010 / Accepted: 14 September 2010 / Published online: 5 October 2010
