Kirwan M.,Queen Mary, University of London |
Walne A.J.,Queen Mary, University of London |
Plagnol V.,University College London |
Velangi M.,Laboratory Haematology |
And 4 more authors.
American Journal of Human Genetics | Year: 2012
Aplastic anemia (AA) and myelodysplasia (MDS) are forms of bone marrow failure that are often part of the same progressive underlying disorder. While most cases are simplex and idiopathic, some show a clear pattern of inheritance; therefore, elucidating the underlying genetic cause could lead to a greater understanding of this spectrum of disorders. We used a combination of exome sequencing and SNP haplotype analysis to identify causative mutations in a family with a history of autosomal-dominant AA/MDS. We identified a heterozygous mutation in SRP72, a component of the signal recognition particle (SRP) that is responsible for the translocation of nascent membrane-bound and excreted proteins to the endoplasmic reticulum. A subsequent screen revealed another autosomal-dominant family with an inherited heterozygous SRP72 mutation. Transfection of these sequences into mammalian cells suggested that these proteins localize incorrectly within the cell. Furthermore, coimmunoprecipitation of epitope-tagged SRP72 indicated that the essential RNA component of the SRP did not fully associate with one of the SRP72 variants. These results suggest that inherited mutations in a component of the SRP have a role in the pathophysiology of AA/MDS, identifying a third pathway for developing these disorders alongside transcription factor and telomerase mutations. © 2012 by The American Society of Human Genetics. All rights reserved.
Danise P.,Laboratory Haematology |
Rovetti A.,Laboratory Haematology |
Avino D.,Laboratory Haematology |
Di Palma A.,Laboratory Haematology |
And 2 more authors.
International Journal of Laboratory Hematology | Year: 2013
Introduction: Haematological analysis of body fluids (BF) specimens can provide clinicians with valuable diagnostic information because it can indicate one of several serious medical conditions. Although up to now the microscopic counting and the differentiation of WBC in a BF smear have been used as a reference. The introduction of semiautomated and automated methods of analysis has reduced interoperator variability and improved turnaround time and precision. The aim of our study was to evaluate the accuracy and the correlation between the three methods and with the reference method. Methods: We examined 110 body fluid samples. Total counting of each sample has been conducted with all systems: Pentra DX120, ADVIA 2120 and XE-2100 and the manual method. Results: We found statistically significant correlation between the data obtained in the ascitic and pleuric liquid but not in the cerebrospinal fluid. Conclusion: The introduction of automated method for BF analysis is more and more useful in the routine job of a laboratory analysis. It is therefore very important to evaluate the performance of the different automated haematology technologies, because there is a lack of literature in this field. The comparison between the Pentra DX 120, the other technologies and the manual counting showed instrumental overlapping capabilities. © 2013 John Wiley & Sons Ltd.