Walne, AJ and Dokal, A and Plagnol, V and Beswick, R and Kirwan, M and de la Fuente, J and Vulliamy, T and Dokal, I (2012) Exome sequencing identifies MPL as a causative gene in familial aplastic anemia. Haematologica , 97 (4) 524 - 528. 10.3324/haematol.2011.052787.
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The primary cause of aplastic anemia remains unknown in many patients. The aim of this study was to clarify the genetic cause of familial aplastic anemia. Genomic DNA of an affected individual from a multiplex consanguineous family was hybridized to a Nimblegen exome library before being sequenced on a GAIIx genome analyzer. Once the disease causing homozygous mutation had been confirmed in the consanguineous family, this gene was then analyzed for mutation in 33 uncharacterized index cases of aplastic anemia (<13 years) using denaturing HPLC. Abnormal traces were confirmed by direct sequencing. Exome sequencing identified a novel homozygous nonsense mutation in the thrombopoietin receptor gene MPL. An additional novel homozygous MPL mutation was identified in the screen of 33 aplastic anemia patients. This study shows for the first time a link between homozygous MPL mutations and familial aplastic anemia. It also highlights the important role of MPL in trilineage hematopoiesis.
|Title:||Exome sequencing identifies MPL as a causative gene in familial aplastic anemia.|
|Additional information:||PMCID: PMC3347658|
|Keywords:||Anemia, Aplastic, Child, Preschool, Consanguinity, Exome, Family, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Mutation, Pedigree, Receptors, Thrombopoietin, Sequence Analysis, DNA, Telomere|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute|
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