Inherited Interleukin 2-Inducible T-Cell (ITK) Kinase Deficiency in Siblings With Epidermodysplasia Verruciformis and Hodgkin Lymphoma.

Biallelic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)-lymphoproliferative disorders. We describe a novel association of a homozygous ITK mutation with ß-human papillomavirus (HPV)-positive epidermodysplasia verruciformis. Thus, loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including ß-HPV and EBV.

Long--Term Free Survival of Two Class III ß-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation.

At present, hematopoietic stem cell transplantation is the only curative treatment for ß thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III ß thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III ß thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk ß-thalassemia patients.

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.