Congenital amegakaryocytic thrombocytopenia—Report of a new <i>c‐mpl</i> gene missense mutation

Passos‐Coelho, José Luís; Sebastião, M.; Gameiro, Paula; Reichert, Anja; Vieira, Luı́s; Ferreira, I.; Miranda, Noel F C C de; Guimarães, André Vicente; Leal-da-Costa, F.; Abecasis, Manuel

doi:10.1002/ajh.20756

Cited by 18 publications

(15 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1,[4][5][6][7][8][9][10][11] However, the diagnosis of five patients in two centers during the last 2 years raises the suspicion that the incidence of the disease is underestimated, presumably because the initial presentation of CAMT with isolated thrombocytopenia can be easily misdiagnosed with idiopathic thrombocytopenic purpura, while the late pancytopenic phase is indistinguishable from aplastic anemia. Thus, bone marrow examination should be part of the diagnostic work-up in all children with severe thrombocytopenia since birth and screening of the c-MPL gene should be performed when a reduced number of megakaryocytes is observed.…”

Section: Discussionmentioning

confidence: 99%

“…3 At least 28 different c-MPL mutated alleles have been so far identified from 32 unrelated CAMT families. 1,[4][5][6][7][8][9][10][11] Beside these mutations associated with CAMT, a gain-of-function mutation of c-MPL is responsible for familial essential thrombocythemia. 12 Interestingly, different types of mutations have been associated with different phenotypes, allowing patients to be subdivided into two groups.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Savoia¹,

Dufour²,

Locatelli³

et al. 2007

Haematologica

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVES: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL). Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. To improve our knowledge in this field, we studied clinical and biological features of five new patients. DESIGN AND METHODS: We diagnosed five CAMT patients, identified c-MPL mutations, including five novel alterations and investigated relationships between mutations and their clinical-biological consequences. RESULTS: In all cases, platelet c-MPL and bone marrow colonies were reduced, while serum TPO levels were elevated. We also documented that the percentage of bone marrow cells expressing tumor necrosis factor-a and interferon-g was increased during pancytopenia as compared to in controls, suggesting that, as in other bone marrow failure diseases, these inhibitory cytokines contributed to the pancytopenia. Contrary to previously published data, we found no evidence of correlations between different types of mutations and the clinical course. INTERPRETATION AND CONCLUSIONS: These results suggest that therapies, such as hematopoietic stem cell transplantation, which are potentially curative although associated with a risk of treatment-related mortality, should not be postponed even in those CAMT patients whose c-MPL mutations might predict residual activity of the TPO receptor

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Savoia¹,

Dufour²,

Locatelli³

et al. 2007

Haematologica

View full text Add to dashboard Cite

show abstract

“…A small number of patients was asymptomatic at birth and presented with signs of thrombocytopenia or pancytopenia in childhood (Gandhi et al , 2005; Passos‐Coelho et al , 2007; Savoia et al , 2007; Steinberg et al , 2007). Therefore, the diagnosis of CAMT has to be taken into account even in those cases that first present with thrombocytopenia or aplastic anaemia after the first year of life.…”

Section: The Clinical Presentation Of Camtmentioning

confidence: 99%

Advances in the understanding of congenital amegakaryocytic thrombocytopenia

Ballmaier

Germeshausen

2009

Br J Haematol

View full text Add to dashboard Cite

SummaryCongenital amegakaryocytic thrombocytopenia (MIM #604498) is an extremely rare inherited bone marrow failure syndrome, usually presenting as a severe thrombocytopenia at birth due to ineffective megakaryocytopoiesis and no characteristic physical anomalies. Usually the isolated thrombocytopenia progresses to pancytopenia during the first years of life. The only curative therapy to date is haematopoietic stem cell transplantation. Most of the cases of congenital amegakaryocytic thrombocytopenia are caused by defective expression or function of the thrombopoietin receptor due to homozygous or compound heterozygous mutations in the gene MPL. The essential roles of thrombopoietin as a lineage specific regulator of platelet production and as a regulator of haematopoietic stem cell function are reflected in the haematological defects seen in affected individuals.

show abstract

“…Review of the literature identified nine cases of unrelated SCT in patients with CAMT with detailed transplant information (Table 1) (5, 8, 9, 12–14). Four additional cases were identified that have incomplete details on the age at time of transplant, HLA matching, preparative regimens and were not included in this review (15–18). All nine patients except one received a fully ablative preparative regimen with five receiving TBI.…”

Section: Discussionmentioning

confidence: 99%

Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

Frangoul

Keates-Baleeiro

Calder

et al. 2010

Pediatric Transplantation

View full text Add to dashboard Cite

CAMT is a very rare cause of thrombocytopenia in infants. Most of the patients will progress to marrow failure. Allogeneic stem cell transplant remains the only curative therapy. We present two patients with CAMT who underwent an unrelated donor bone marrow transplant, one after developing marrow failure and another early in the course of the disease. Both patients tolerated the transplant with minimal toxicity and durable engraftment. We also present a comprehensive review of the literature for unrelated donor transplant for this condition.

show abstract

Congenital amegakaryocytic thrombocytopenia—Report of a new c‐mpl gene missense mutation

Cited by 18 publications

References 5 publications

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations

Advances in the understanding of congenital amegakaryocytic thrombocytopenia

Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

Contact Info

Product

Resources

About