Merck
  • Início
  • Resultados da busca
  • Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia.

Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia.

Blood (2013-10-03)
Majed J Dasouki, Syed K Rafi, Adam J Olm-Shipman, Nathan R Wilson, Sunil Abhyankar, Brigitte Ganter, L Mike Furness, Jianwen Fang, Rodrigo T Calado, Irfan Saadi
RESUMO

We recently identified 2 siblings afflicted with idiopathic, autosomal recessive aplastic anemia. Whole-exome sequencing identified a novel homozygous missense mutation in thrombopoietin (THPO, c.112C>T) in both affected siblings. This mutation encodes an arginine to cysteine substitution at residue 38 or residue 17 excluding the 21-amino acid signal peptide of THPO receptor binding domain (RBD). THPO has 4 conserved cysteines in its RBD that form 2 disulfide bonds. Our in silico modeling predicts that introduction of a fifth cysteine may disrupt normal disulfide bonding to cause poor receptor binding. In functional assays, the mutant-THPO-containing media shows two- to threefold reduced ability to sustain UT7-TPO cells, which require THPO for proliferation. Both parents and a sibling with heterozygous R17C change have reduced platelet counts, whereas a sibling with wild-type sequence has normal platelet count. Thus, the R17C partial loss-of-function allele results in aplastic anemia in the homozygous state and mild thrombocytopenia in the heterozygous state in our family. Together with the recent identification of THPO receptor (MPL) mutations and the effects of THPO agonists in aplastic anemia, our results have clinical implications in the diagnosis and treatment of patients with aplastic anemia and highlight a role for the THPO-MPL pathway in hematopoiesis in vivo.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Anti-THPO (C-term) antibody produced in rabbit, saturated ammonium sulfate (SAS) precipitated, buffered aqueous solution
Sigma-Aldrich
TPO human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
Anti-THPO antibody produced in rabbit, affinity isolated antibody
Supelco
L-Cystine, certified reference material, TraceCERT®
Sigma-Aldrich
L-Cystine, produced by Wacker Chemie AG, Burghausen, Germany, ≥98.5%
Sigma-Aldrich
L-Cystine, from non-animal source, meets EP testing specifications, suitable for cell culture, 98.5-101.0%
SAFC
L-Cystine
Sigma-Aldrich
L-Cystine, ≥99.7% (TLC)
Sigma-Aldrich
L-Cystine, ≥98% (TLC), crystalline
SAFC
L-Cystine
Cystine, European Pharmacopoeia (EP) Reference Standard