title: Congenital amegakaryocytic thrombocytopenia-3 novel c-MPL mutations and their phenotypic correlations.
abstract: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare bone marrow failure syndrome associated with thrombocytopenia and a tendency to progress to aplastic anemia. Mutations in the c-MPL gene encoding for thrombopoietin receptor have been identified in the majority of the patients. Previous studies suggest a genotype-phenotype correlation wherein the severity of the disease depends on the type of mutation present and residual thrombopoietin receptor activity. The present study describes the clinical and genetic findings on a series of 7 patients with CAMT, 3 of them siblings. The patients were homozygous for 5 mutations in the c-MPL gene, including 3 unique ones: c.212+5G>A, C76T, and G1162C. The clinical picture was variable; 1 patient who was homozygous for a nonsense mutation in exon 1 (C76T) developed infantile acute lymphoblastic leukemia, whereas patients who were homozygous for a splice-site mutation (c.212+5G>A) expressing both normal and mutated transcripts had a milder clinical course. As previously suggested, c-MPL mutation analysis in CAMT patients helps to predict the clinical course and to provide optimal therapy.
authors: Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Isreal.
authors: Orna
authors: O
authors: Steinberg
authors: Gil
authors: G
authors: Gilad
authors: Orly
authors: O
authors: Dgany
authors: Tatyana
authors: T
authors: Krasnov
authors: Meira
authors: M
authors: Zoldan
authors: Ruth
authors: R
authors: Laor
authors: Joseph
authors: J
authors: Kapelushnik
authors: Herzel
authors: H
authors: Gabriel
authors: Chaim
authors: C
authors: Churi
authors: Jerry
authors: J
authors: Stein
authors: Isaac
authors: I
authors: Yaniv
authors: Hannah
authors: H
authors: Tamary
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007557:Israel; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D009154:Mutation; D010641:Phenotype; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013926:Thrombopoietin / Q000235:genetics*
chemical_list: D004247:DNA; D013926:Thrombopoietin